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  • 1980-1984  (1,040)
  • 1920-1924
  • Rat  (616)
  • pharmacokinetics  (424)
  • 1
    Electronic Resource
    Electronic Resource
    Behavioural responsiveness to muscimol and apomorphine 2 months after prolonged treatment with estradiol in rats (1984)
    Springer
    Psychopharmacology 84 (1984), S. 287-288 
    Details
    ISSN: 1432-2072
    Keywords: Prolonged estradiol treatment ; Behaviour ; Rat ; Muscimol ; Apomorphine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two months after prolonged administration of estradiol (ES) in female rats the behavioural responsiveness to muscimol, a GABA receptor stimulating agent, and to apomorphine, a dopamine receptor agonist, was significantly altered. In particular, the decrease in locomotor activity induced by a challenge dose of muscimol (0.5–1 mg/kg) was significantly attenuated in ES-pretreated animals. Conversely, the intensity of stereotyped behaviour elicited by a challenge dose of apomorphine (1 mg/kg) was significantly increased in ES-pretreated rats. The behavioural alterations in the response to muscimol and apomorphine presumably result from the production of central GABA receptor subsensitivity and dopamine receptor supersensitivity respectively, induced by the prolonged ES administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427462
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  • 2
    Electronic Resource
    Electronic Resource
    The effects of proglumide on morphine induced motility changes (1984)
    Springer
    Psychopharmacology 84 (1984), S. 541-543 
    Details
    ISSN: 1432-2072
    Keywords: Morphine ; Cholecystokinin ; Proglumide ; Locomotion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Proglumide (0.02 mg/kg), a cholecystokinin antagonist, was administered to rats either together with or without morphine (0, 5, 15, or 45 mg/kg). Whereas proglumide in the absence of morphine showed a trend towards enhanced behavioral activation, it potentiated the hy[okinesia induced by morphine. These results are consistent with the hypothesis that endogenous cholecystokinin tonically antagonizes opiate modulation of motility, irrespective of whether such modulation is produced by opiates and endogenous or exogenous origin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431463
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  • 3
    Electronic Resource
    Electronic Resource
    Reinforcing properties of morphine and naloxone revealed by conditioned place preferences: a procedural examination (1984)
    Springer
    Psychopharmacology 82 (1984), S. 241-247 
    Details
    ISSN: 1432-2072
    Keywords: Opiates ; Morphine ; Naloxone ; Conditioned place preference ; Reward ; Reinforcement ; State-dependent learning ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In rats, conditioned place preferences are produced by morphine and conditioned place aversions produced by naloxone. In the present studies, several issues concerning the demonstration and interpretation of place conditioning findings were examined in a two-compartment (black and white) tilt box: (1) the responses of naive rats to testing, (2) place conditioning in rats with strong unconditioned biases to one of the sides, and (3) modifications of the testing situation so that naive rats respond to the black and white sides with a minimum of initial bias. Experiments involving manipulation of the conditions of training and testing, use of pentobarbital, and use of a three-compartment test box helped to control for morphine's ability to produce state dependent learning as an explanation of its conditioned place preference. In addition, we examined previous place conditioning studies that failed to show aversive effects of naloxone. These negative findings were suggested to be due to the use or procedures insensitive to aversive stimuli and to the IP administration of naloxone. Finally, in the course of the experiments, novel data on general parameters of the place conditioning were provided. Dose-response curves for subcutaneous (SC) morphine (0.04–5.0 mg/kg) and naloxone (0.02–5.0 mg/kg) were established. Conditioned preferences were also shown to occur after at three pairings of SC drug, and they were retained for at least 1 month.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427782
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  • 4
    Electronic Resource
    Electronic Resource
    Evaluation of the β-carboline ZK 93 426 as a benzodiazepine receptor antagonist (1984)
    Springer
    Psychopharmacology 83 (1984), S. 249-256 
    Details
    ISSN: 1432-2072
    Keywords: ZK 93426 ; Ro 15-1788 ; CGS 8216 ; Benzodiazepine receptor agonists ; Benzodiazepine receptor antagonist ; Benzodiazepine receptor inverse agonist ; Rat ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We describe here biochemical and pharmacological effects of the β-carboline ZK 93426, a new and potent benzodiazepine (BZ) receptor antagonist. ZK 93426 was compared with Ro 15-1788 and CGS 8216, two compounds previously described as BZ receptor antagonists. Certain effects of ZK 93426, Ro 15-1788 and CGS 8216 were quite similar (e.g., 3H-FNM displacement, “GABA ratio”, “photo-shift”). In most pharmacological tests ZK 93426 and Ro 15-1788 lacked overt effects; Ro 15-1788 was a weak agonist in some paradigms, while ZK 93426 exhibited a potent proconflict effect but also a weak anticonvulsant effect. This interesting finding with ZK 93426 suggests that BZ receptor ligands may possess differential efficacy at BZ receptor subtypes. In contrast, CGS 8216 exhibited potent proconvulsant effects in several paradigms in addition to proconflict and pentylenetetrazol generalizing effects. ZK 93426, Ro 15-1788 and CGS 8216 were almost equally potent as antagonists of the effects of BZ receptor agonists, such as diazepam and lorazepam. However, ZK 93426 was the most potent inhibitor of the convulsions produced by the BZ receptor inverse agonist DMCM.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00464789
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  • 5
    Electronic Resource
    Electronic Resource
    Long term effects of chronic chlordiazepoxide (CDP) administration (1984)
    Springer
    Psychopharmacology 83 (1984), S. 277-280 
    Details
    ISSN: 1432-2072
    Keywords: Chlordiazepoxide ; Metrazol ; Audiogenic seizures ; Resistance to extinction ; Resistance to punishment ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three experiments were carried out to test the long-term behavioral effects of 12 days administration of CDP (5 mg/kg/day) in rats. In the first two experiments, 4 weeks after the end of drug administration (CDP or placebo), and after 2 weeks of training to run a straight alley for food reward, animals were tested in extinction, i.e., following omission of reward (Expt. 1) or with punishment, i.e., 0.3 mA electric shock in addition to the food reward (Expt. 2). Drug-treated animals showed significantly increased resistance to extinction and to punishment compared with controls. In the third experiment, 10 weeks after drug administration, animals were exposed to 60 s of intense noise to induce audiogenic seizures. The convulsant metrazol was injected 5 min prior to successive sessions (10 min apart) with doses starting at 10 mg/kg and increased by 10 mg/kg each session up to 40 mg/kg. Drug-treated animals were significantly less susceptible to seizures than their placebo controls. These results suggest that chronic benzodiazepine treatment causes long-term neurochemical changes which are responsible for the observed behavioral effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00464794
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  • 6
    Electronic Resource
    Electronic Resource
    6-Hydroxydopamine lesion of the dopamine mesocorticolimbic cell bodies increases (+)-amphetamine self-administration (1984)
    Springer
    Psychopharmacology 83 (1984), S. 281-284 
    Details
    ISSN: 1432-2072
    Keywords: (+)-Amphetamine ; Self-administration ; Dopaminergic neurons ; Acquisition ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of 6-OHDA lesions of the dopaminergic mesocorticolimbic cell bodies on intravenous (+)-amphetamine self-administration in the rat was assessed. An acquisition paradigm was used in which the rat had to discriminate between an active and an inactive lever. Each press on the active lever delivered 7.5 μg/kg (+)-amphetamine. The lesioned animals acquired this discrimination faster and hence self-administered a larger amount of drug. Thus dysfunction of dopaminergic neurons can induce an enhanced vulnerability to drugs which may be abused by humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00464795
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  • 7
    Electronic Resource
    Electronic Resource
    Opioid peptides and self-stimulation of the medial prefrontal cortex in the rat (1984)
    Springer
    Psychopharmacology 83 (1984), S. 288-292 
    Details
    ISSN: 1432-2072
    Keywords: Intracranial self-stimulation ; Enkephalins ; Morphine ; Naloxone ; Prefrontal cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The possible involvement of opioid peptides as part of the neurochemical substrates of self-stimulation (SS) in the medial prefrontal cortex (MPC) of the rat was investigated in two different groups of rats bilaterally implanted with monopolar electrodes in the MPC. In the first group, morphine (5, 10 and 20 μg) and an enkephalin analogue (BW 180) (5, 10, 20 and 40 μg) and an enkephalin analogue (BW 180) (5, 10, 20 and 40 μg) were injected through cannulae implanted into the lateral ventricles (IV). In the second group, naloxone (0.04, 0.4, and 1.6 μg) and morphine (5, 10 and 20 μg) were injected through cannulae implanted into the MPC, 1.5 mm above the tip of the stimulating electrodes. In the first group, spontaneous motor activity (SMA) was measured as a control for non-specific effects (sedation or motor dysfunction). In the second group SS, contralateral to the microinjected side, served as control. SS and SMA were measured 1 and 2 h postinjection. One hour after IV injection of morphine SS was not affected, although SMA was decreased. Two hours postinjection, on the contrary, SS was increased while SMA remained decreased. Similar effects were found with IV microinjections of BW 180. Naloxone, intraperitoneally injected, reversed all these effects. Naloxone or morphine injected intracerebrally (MPC) produced no changes in SS either in the injected or in the contralateral side, which served as control. The present results suggest that the effects found with IV injections of opioids on SS of the MPC are indirect (through activation of other brain areas) and not mediated by a direct action on the neurochemical substrates underlying this behaviour in the MPC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00464797
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  • 8
    Electronic Resource
    Electronic Resource
    A study of the effects of clonidine on the EEG in rats treated with single and multiple doses of antidepressants (1984)
    Springer
    Psychopharmacology 84 (1984), S. 85-90 
    Details
    ISSN: 1432-2072
    Keywords: Antidepressants ; Clonidine ; EEG activity ; Clonidine-antidepressants interaction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of repeated and single administrations of desipramine, amitryptiline, and mianserin on the EEG effects of clonidine has been investigated in rats implanted with chronic cortical electrodes. Clonidine induced a dose-dependent EEG synchronization in control animals. Signs of behavioral depression occurred after administration of moderate (0.1 mg/kg) and higher (0.2 mg/kg) doses of clonidine. Single doses of desipramine and amitryptiline attenuated the clonidine effect, while mianserine potentiated clonidine-induced synchronization. Antidepressants given once daily for 14 days completely (desipramine and amitryptiline) or partially (mianserin) reduced the effect of clonidine. Antidepressants alone produced only a slight effect on cortical EEG pattern.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432031
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  • 9
    Electronic Resource
    Electronic Resource
    Environmental experience produces qualitative changes in the stimulant effects of β-phenylethylamine in rats (1984)
    Springer
    Psychopharmacology 84 (1984), S. 132-135 
    Details
    ISSN: 1432-2072
    Keywords: β-Phenylethylamine ; Locomotor activity ; Rearing-stereotypy ; Environmental experience ; Amphetamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of β-phenylethylamine (PEA 6.25, 12.5, and 25.0 mg/kg IP) on spontaneous motor activity were examined in rats before (novel situation) and after (familiar situation) they had experience of the test environment, in an undrugged state. In a novel cage, 12.5 mg/kg PEA stimulated rearing and locomotion. A dose of 25.0 mg/kg PEA also increased rearing and produced stereotyped head movements, but did not increase locomotion, in a novel environment. In a familiar cage, both 12.5 and 25.0 mg/kg PEA stimulated locomotion and sniffing, whereas rearing was unaffected by PEA treatment under these conditions. These data provide a striking instance of a qualitative change in the behavioural response to a psychostimulant compound which is associated with the relative familiarity of the animal with the test environment. In addition, the results show that PEA induces stereotypy at high doses and increases locomotor activity at moderate doses, which is a further illustration of the similarity in the unconditioned behavioural effects of PEA and amphetamine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432042
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  • 10
    Electronic Resource
    Electronic Resource
    Self-injection of diazepam in naive rats: Effects of dose, schedule and blockade of different receptors (1984)
    Springer
    Psychopharmacology 84 (1984), S. 174-177 
    Details
    ISSN: 1432-2072
    Keywords: Schedule-induced self-injection ; Diazepam ; Benzodiazepine ; Ro 15-1788 ; Bicuculline ; Haloperidol ; Naloxone ; Dopamine ; GABA ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present series of experiments had two main objectives: The first was to determine the conditions under which self-injection of the benzodiazepine diazepam would be optimal; the second was to identify neurochemical substrates which underlie the maintenance of diazepam selfadministration. Data from the first experiment indicated that rats maintained on an FI-1 (Fixed Interval of 1 min) schedule of food delivery self-injected significantly more diazepam than rats not maintained on this schedule. Results from the second experiment demonstrated that the benzodiazepine antagonist Ro 15-1788, and the GABA antagonist bicuculline, significantly reduced diazepam self-administration, but the opiate antagonist naloxone was without effect. Data from the third experiment showed that the dopamine antagonist haloperidol also significantly reduced the rate of diazepam self-injection. Thus, these findings indicate that the acquisition of diazepam self-injection occurs under an FI-1 schedule of food delivery, which has been shown to be middly stressful, while its maintenance depends upon the functional integrity of benzodiazepine and GABA receptors and upon the activity of deopaminergic pathways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427442
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  • 11
    Electronic Resource
    Electronic Resource
    The effect of acute zimeldine and alaproclate administration on the acquisition of two-way active avoidance: Comparison with other antidepressant agents, test of selectivity and sub-chronic studies (1984)
    Springer
    Psychopharmacology 84 (1984), S. 188-195 
    Details
    ISSN: 1432-2072
    Keywords: Zimeldine ; Alaproclate ; Antidepressants ; PCA ; Selectivity ; Subchronic administration ; Two-way ; One-way ; Avoidance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The dose-dependent effect of acute zimeldine and alaproclate treatment upon the acquisition of two-way and one-way active avoidance in the rat was studied in a single-session and in a repeated-sessions design. Zimeldine (5–20 mg/kg, IP), but not alaproclate, caused disruptions of two-way avoidance acquisition. Acquisition deficits were also caused by citalopram and fluoxetine but not the other antidepressant drugs tested. Zimeldine, but not alaproclate or desipramine, caused a slight but non-significant impairment of one-way active avoidance; neither zimeldine nor alaproclate produced any effects upon fear conditioning and retention testing. The long-term action of p-chloroamphetamine (2×10 mg/kg) antagonised the acute zimeldine effect totally, and chronic treatment with zimeldine (15 days, 1×50 μmol/kg) and chlorimipramine (15 days, 2×10 μmol/kg) also caused some partial blockade of the two-way avoidance deficit. These data seem to suggest some involvement of serotonin (5-HT) in the observed disruptions of two-way active avoidance caused by acute zimeldine treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427444
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  • 12
    Electronic Resource
    Electronic Resource
    Species differences in the relative analgesic potencies of some classical opiates and opioid peptides (1984)
    Springer
    Psychopharmacology 82 (1984), S. 400-402 
    Details
    ISSN: 1432-2072
    Keywords: Opiates ; Opioid peptides ; Enkephalin analogues ; β-Endorphin ; Analgesia ; Species differences ; Morphine ; d-Met2, Pro5-enkephalinamide ; Rat ; Mouse ; Opiate receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The analgesic ED50 values of some classical morphine congeners (morphine, methadone, fentanyl, azidomorphine) in the rat and mouse tail-flick tests were found to be similar. However, several synthetic derivatives of the natural enkephalins were more potent in mice than in rats. (These analogs contain d-amino acid in position 2 and d- or l-sulfonic (or phosphonic) acid residue in position 5). β-Endorpin, d-Met2, Pro5-enkephalinamide and two partial agonists showed intermediate interspecies relative potencies. According to the data obtained, similar opiate receptors might mediate the analgesic action of classical opiates in rats and in mice. However, the opiate receptors responsible for the antinociceptive effects of the above mentioned enkephalin analogues must be dissimilar in the two species examined. The results are discussed in terms of the role of μ- and δ-receptors in mediation of the analgesic effect induced by different types of opioids.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427694
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  • 13
    Electronic Resource
    Electronic Resource
    Dopaminergic behaviour stereospecifically promoted by the D1 agonist R-SK & F 38393 and selectively blocked by the D1 antagonist SCH 23390 (1984)
    Springer
    Psychopharmacology 82 (1984), S. 409-410 
    Details
    ISSN: 1432-2072
    Keywords: Dopamine D1 & D2 receptors ; SK & F 38393 ; SCH 23390 ; Grooming ; Behaviour ; Stereotypy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The selective D1 dopamine receptor agonist R-SK & F 38393 (20 mg/kg), but not its S-antipode, stereospecifically promoted episodes of prominent grooming behaviour. Typical stereotyped behaviour, such at that induced by apomorphine, was not seen. Grooming responses to 20 mg/kg R-SK & F 38393 were blocked by 0.1–0.5 mg/kg of the selective D1 antagonist SCH 23390 but not by 1.0–5.0 mg/kg of the selective D2 antagonist metoclopramide, while stereotyped behaviour induced by 0.5 mg/kg apomorphine was blocked by both antagonists. These results are consistent with certain individual dopaminergic behaviours such as grooming being mediated by D1 receptors. Other dopaminergic syndromes may involve complex functional interactions between D1 and D2 receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427697
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  • 14
    Electronic Resource
    Electronic Resource
    The effects of exposure to diazepam during various stages of gestation or during lactation on the development and behavior of rat pups (1984)
    Springer
    Psychopharmacology 83 (1984), S. 51-55 
    Details
    ISSN: 1432-2072
    Keywords: Diazepam ; Prenatal ; Early postnatal treatment ; Learning disabilities ; Hyperactivity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present study we have investigated the effects of diazepam (DZP) (10 mg/kg) treatment of rat dams during different periods of gestation or during lactation on the development and behavior of their offspring. The results show that DZP exposure during different phases of early development has differing effects on later behavior. Exposure during mid-gestation resulted in early and transient hyperactivity, but no learning or memory deficits at 2 months of age were observed. However, both late prenatal and early postnatal exposure to DZP resulted in significant behavioral changes. Late prenatal treatment caused no hyperactivity but resulted in poor performance on the learning and retention of a choice discrimination task, while early postnatal exposure resulted in consistent and lasting hyperactivity and in substantial discrimination learning and retention deficits at 2 months of age.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427422
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  • 15
    Electronic Resource
    Electronic Resource
    Passive avoidance in rats: Disruption by dopamine applied to the nucleus accumbens (1984)
    Springer
    Psychopharmacology 83 (1984), S. 70-75 
    Details
    ISSN: 1432-2072
    Keywords: Dopamine ; Locomotor activity ; Nucleus accumbens ; Passive avoidance ; State-dependent learning ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The acquisition of a one-trial step-through passive avoidance task was examined in rats following the administration of nialamide IP and dopamine (DA) or saline into the nucleus accumbens. DA-treated rats displayed impaired learning of the task as evidenced by their lower step-through latencies on a retest trial 7 days later. The specificity of this impairment was studied in a 2×2 design involving intracerebral injections prior to both training and testing trials. It was found that DA treatment prior to the training trial disrupted learning or memorization of the task but that DA did not affect performance or retrieval and did not induce state-dependent learning. These findings suggest that DA applied to the nucleus accumbens does not facilitate learning per se.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427425
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  • 16
    Electronic Resource
    Electronic Resource
    Acquisition of behaviourally augmented tolerance to ethanol and its relationship to muscarinic receptors (1984)
    Springer
    Psychopharmacology 83 (1984), S. 88-92 
    Details
    ISSN: 1432-2072
    Keywords: Ethanol ; Behaviourally augmented tolerance ; Physiological tolerance ; Muscarinic receptor ; Operant conditioning ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two groups of adult male rats were injected daily with ethanol (1.5 g/kg IP in 15% w/v solution) either before (the behaviourally augmented tolerant group) or after (the physiologically tolerant group) being placed in operant chambers. The control groups received daily isotonic saline injections either before or after the operant task. When challenged with ethanol (2.5 g/kg) on day 30 prior to the operant task, the control group was most impaired, while the behaviourally augmented tolerant group was significantly less impaired than the physiologically tolerant group. The two ethanol-treated groups were impaired to the same extent when challenged on day 60. Partial generalization of this behavioural tolerance to ethanol was observed, as the behaviourally augmented tolerant group was less impaired than the physiologically tolerant group for a tail flick response to painful stimuli after an ethanol challenge on day 30. However, the two ethanol-treated groups exhibited similar impairments of locomotor activity after an ethanol challenge on day 40. No differences in muscarinic receptor binding among the control and two ethanol-treated groups were found. These findings demonstrate that behaviourally augmented tolerance to ethanol may be partially generalizable but is unrelated to changes in muscarinic cholinergic receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427429
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  • 17
    Electronic Resource
    Electronic Resource
    Naloxone suppresses fluid consumption in tests of choice between sodium chloride solutions and water in male and female water-deprived rats (1984)
    Springer
    Psychopharmacology 84 (1984), S. 362-367 
    Details
    ISSN: 1432-2072
    Keywords: Opiates ; Naloxone ; Sodium preference ; Saline consumption ; Thirst ; Sex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of naloxone on fluid consumption by water-deprived rats trained to choose between a saline solution and water in a 15-min drinking test were examined. Rats of each sex were allocated to three groups and given access to 0.125% NaCl, 0.6% NaCl, and 1.7% NaCl, respectively, as the alternative to water. Under control conditions they drank substantially more of the hypotonic salt solutions than water, but drank slightly more water than hypertonic salt solution. Naloxone generally reduced fluid consumption, dose-dependently (0.01–10 mg/kg). In the cases of the two hypotonic solutions, the suppressant effect of naloxone was limited to saline solution. The usually low levels of water consumption were unaffected. In the case of the hypertonic solution, naloxone suppressed salt and water intakes by equivalent amounts. The effects of naloxone in the tests with the two higher salt concentrations depended upon sex. There was one example of a significant naloxone-induced reduction in saline preference (females; 0.125% NaCl v H2O). In other instances, saline preferences were not significantly modified. The results are briefly discussed in relation to current suggestions that naloxone may affect fluid consumption in ways which are taste-dependent (e.g., taste sensitivity, palatability, reward). An alternative view is also considered, that the effects of naloxone may be taste-independent, at least in the particular case of drinking in a two-choice test with saline and water.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00555214
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  • 18
    Electronic Resource
    Electronic Resource
    A pharmacokinetic study of CGS-8216, a benzodiazepine receptor ligand, in the rat (1984)
    Springer
    Psychopharmacology 84 (1984), S. 420-422 
    Details
    ISSN: 1432-2072
    Keywords: CGS-8216 ; Benzodiazepine ; Plasma ; Pharmacokinetics ; Rat ; Brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A rapid and sensitive method is described for the determination of CGS-8216 (a pyrazoloquinoline that displaces benzodiazepines from their binding sites in the brain but which reverses some of the behavioural actions of the benzodiazepines) in plasma using high-performance liquid chromatography with ultraviolet detection. CGS-9896 serves as the internal standard. The method is applied to a pharmacokinetic study of CGS-8216 in the rat. CGS-8216 was not detectable in plasma 24 h after a single IP administration of a 10 mg/kg dose. Animals treated with five once-daily injections of CGS-8216 had plasma concentrations 30 min after the final injection that were approximately four-times those observed 30 min after a single treatment. This suggests that caution must be used in the interpretation of results from experiments using multiple administrations of CGS-8216. The compound could not be detected in brain tissue at any of the time points studied.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00555224
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  • 19
    Electronic Resource
    Electronic Resource
    Repeated stress increases locomotor response to amphetamine (1984)
    Springer
    Psychopharmacology 84 (1984), S. 431-435 
    Details
    ISSN: 1432-2072
    Keywords: Stress ; Amphetamine ; Locomotor activity ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adult male rats submitted to mild, 20 min electric foot shock sessions for 10 days displayed an enhanced locomotor response to 0.75 mg/kg (+)amphetamine 24 h after the last shock session, when compared to non-stressed controls. This effect was still present in rats specifically deprived of their forebrain noradrenergic innervation, suggesting the involvement of a dopaminergic mechanism. Cortical and limbic dopamine turnover which increased immediately after acute and repeated foot shocks returned to normal 24 h later, at the time of the pharmacological testing. This fact indicates that a permanent modification of the basal DA activity is not responsible for the above effect apomorphine was enhanced in experimental animals, while hypoactivity resulting from the injection of 0.05 mg/kg apomorphine was similar in control and shocked rats. This latter result suggests the existence of an increased postsynaptic DA sensitivity as a result of repeated stress.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00555227
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  • 20
    Electronic Resource
    Electronic Resource
    Effects of (-)3-PPP on acquisition and retention of a conditioned avoidance response in the rat (1984)
    Springer
    Psychopharmacology 84 (1984), S. 441-445 
    Details
    ISSN: 1432-2072
    Keywords: Conditioned avoidance ; Dopamine autoreceptors ; 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP) ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The administration of (-)3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP) was found to partially, but significantly, suppress the acquisition (4–8 mg/kg IP) and performance (8–16 mg/kg IP) of a conditioned avoidance response (CAR) in male Sprague-Dawley rats. All statistically significant effects were observed within 2 h of injection. Furthermore, using a situation in which the CAR was dependent on a visual successive discrimination, it was shown that discriminative performance was unaffected, and that (-)3-PPP (12.5–25 mg/kg IP) but not (+)3-PPP, suppressed the CAR. When (-)3-PPP (6.25 mg/kg IP) was combined with haloperidol (0.1–0.4 mg/kg IP), additive effects on the CAR performance were observed. Considering these effects, and the doses of (-)3-PPP required to suppress the CAR performance, it is concluded that the effects obtained in the present experiments are primarily due to a blockade of postsynaptic DA receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431447
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  • 21
    Electronic Resource
    Electronic Resource
    Differential effects of continuous administration for 1 year of haloperidol or sulpiride on striatal dopamine function in the rat (1984)
    Springer
    Psychopharmacology 84 (1984), S. 503-511 
    Details
    ISSN: 1432-2072
    Keywords: Haloperidol ; Sulpiride ; Striatum ; Supersensitivity ; Dopamine receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Administration of haloperidol (1.4–1.6 mg/kg/day) for up to 12 months or sulpiride (102–109 mg/kg/day) for between 6 and 12 months increased the frequency of purposeless chewing jaw movements in rats. N,n-propylnorapomorphine (NPA) (0.25–2.0 mg/kg SC) did not induce hypoactivity in haloperidol-treated rats at any time; sulpiride treatment for 9 and 12 months caused a reduction in the ability of NPA to induce hypoactivity. Haloperidol, but not sulpiride, treatment enduringly inhibited low dose apomorphine effects (0.125 mg/kg SC). After 12 months, sterotypy induced by high doses of apomorphine (0.5–1.0 mg/kg) was exaggerated in haloperidol-, but not sulpiride-treated rats. Bmax for specific striatal 3H-spiperone binding was increased by haloperidol, but not sulpiride, treatment throughout the study. Bmax for 3H-NPA binding was elevated only after 12 months of both haloperidol and sulpiride treatment. Bmax for 3H-piflutixol binding was not alfered by chronic haloperidol or sulpiride treatment. Striatal dopamine-stimulated adenylate cyclase activity was inhibited for the 1st month of haloperidol treatment, thereafter returning to control levels; dopamine stimulation was increased after 12 months of sulpiride treatment. Striatal acetylcholine content was increased after 3 and 12 months of treatment with haloperidol, but was not affected by sulpiride. Chronic administration of sulpiride does not induce identical changes in striatal dopamine function to those caused by haloperidol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431457
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  • 22
    Electronic Resource
    Electronic Resource
    Modification of nigral kainic acid-induced ipsilateral circling behaviour in the rat by neuroleptics and by contralateral caudate ablation (1984)
    Springer
    Psychopharmacology 84 (1984), S. 526-530 
    Details
    ISSN: 1432-2072
    Keywords: Substantia nigra ; Rotational behaviour ; Kainic acid ; Neuroleptics ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A study was performed to examine possible changes in excitatory amino acid sensitivity within the pars reticulata of the rat substantia nigra as a result of neuroleptic exposure. Unilateral application of 20 ng kainic acid into caudal regions of the pars reticulata resulted in ipsilateral circling behaviour. This activity was significantly reduced 7 days after administration of the depot neuroleptic fluphenazine decanoate, 10.0 mg/kg SC, or 1 h after pretreatment with haloperidol, 0.1–1.0 mg/kg IP. The inhibitory effect of 0.1 mg/kg haloperidol was unaffected by prior ablation of the ipsilateral striatum, which by itself had no effect on the kainate-induced response. However, contralateral caudate ablation 21 days prior to intra-nigral kainate resulted in a markedly enhanced response, although 0.1 mg/kg haloperidol appeared to retain its inhibitory action when tested in such animals. The experimental data suggest a compensatory role of contralateral striatal mechanisms in nigral kainate-induced ipsilateral circling behaviour in the rat. Furthermore, they demonstrate at least a modulatory role of central dopaminergic mechanisms in such elicited behaviour. This latter action may involve multiple basal ganglia sites or, more probably, occur in other brain areas such as the mesolimbic system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431460
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  • 23
    Electronic Resource
    Electronic Resource
    Δ 1-tetrahydrocannabinol but not cannabidiol reduces contact and aggressive behavior of rats tested in dyadic encounters (1984)
    Springer
    Psychopharmacology 84 (1984), S. 561-565 
    Details
    ISSN: 1432-2072
    Keywords: Δ 1-Tetrahydrocannabinol (Δ 1-THC) ; Cannabidiol (CBD) ; Social behavior ; Social interactions ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A low and a high dose of Δ 1-Tetrahydrocannabinol (Δ 1-THC) and of cannabidiol (CBD) were IP injected in rats that had been isolated for 7 days. Forty-five minutes after injection, the rats were tested for social interactions with non-isolated, untreated test partners in dyadic encounters under standardized conditions. Different aspects of social behavior were analyzed. The high dose of Δ 1-THC (10 mg/kg) prevented nearly all social interactions. The low dose of Δ 1-THC (1 mg/kg) exerted selective and specific effects on social interactions. Social contact behavior, including crawl over/mounting, and social grooming, and aggressive behavior, including fighting, kicking, and biting, were markedly decreased, whereas social exploratory behavior (exploration of the partner and anogeniaal investigation) and the behavioral item, approach/follow, were hardly affected by Δ 1-THC treatment. Both doses of CBD (2 and 20 mg/kg) failed to change the various aspects of social interaction. It is postulated that the effects of Δ 1-THC on close and intimate contact behavior of rats may contribute to the understanding of marihuana taking in humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431467
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  • 24
    Electronic Resource
    Electronic Resource
    Dorsal bundle lesions do not affect latent inhibition of conditioned suppression (1984)
    Springer
    Psychopharmacology 84 (1984), S. 549-555 
    Details
    ISSN: 1432-2072
    Keywords: Noradrenaline ; Dorsal noradrenergic bundle ; Latent inhibition ; Selective attention ; 6-Hydroxydopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three expreiments are reported which examine the effects of lesions of the dorsal ascending noradrenergic bundle (DB) on latent inhibition using a conditioned suppression procedure in rats. In none of the experiments did the DB lesion have any effect, despite changes in the extent of latent inhibition and in the control procedures used to assess it. The results are discussed in relation to the attentional theory of DB function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431465
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  • 25
    Electronic Resource
    Electronic Resource
    Dissociable effects of 6-OHDA-induced lesions of neostriatum on anorexia, locomotor activity and stereotypy: The role of behavioural competition (1984)
    Springer
    Psychopharmacology 83 (1984), S. 363-366 
    Details
    ISSN: 1432-2072
    Keywords: Amphetamine ; Locomotor activity ; Stereotypy ; Anorexia ; Behavioural competition ; Neostriatum ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of 6-OHDA-induced lesions of neostriatum on locomotor activity, stereotypy and anorexia induced by amphetamine (0.5 mg/kg, 1.5 mg/kg and 5.0 mg/kg IP) was examined. Lesioned rats demonstrated attenuated stereotypy and anorexia but enhanced locomotor activity to amphetamine. Biochemical analysis of dopamine and noradrenaline in specific forebrain areas demonstrated significant dopamine depletion in neostriatum. Dopamine levels in mesolimbic, frontal cortex and hypothalamic areas, and noradrenaline in frontal cortex and hypothalamic areas, were not significantly reduced. The data were interpreted in terms of a response incompatibility hypothesis. It is proposed that stereotyped responses mediated by nigrostriatal dopamine neurones are incompatible with eating. In addition, it is suggested that a second form of competition, at the neuro-anatomical level, occurs between mesolimbic and nigrostriatal systems for motor output pathways and the ultimate expression of behaviour. The role of noradrenaline in amphetamine anorexia is also discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428546
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  • 26
    Electronic Resource
    Electronic Resource
    Central mediation of the conditioned taste aversion induced in rats by harmaline (1984)
    Springer
    Psychopharmacology 83 (1984), S. 384-389 
    Details
    ISSN: 1432-2072
    Keywords: Intracerebral drug application ; Memory ; Neophobia ; Oliva inferior ; Saccharin preference ; Learning under anesthesia ; Cerebellar tremor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The assumption that drugs used as unconditioned stimuli in conditioned taste aversion (CTA) studies act centrally was tested by comparing the effects of systemic and intracerebral injections of harmaline hydrochloride (H) in 340 rats. Intraperitoneal injection of 5–20 mg/kg but not of 2.5 mg/kg H administered 5 min after 15-min saccharin (0.1%) drinking decreased saccharin-water preference in a two-choice retention test, performed 48 h later, from 55% to 20%. Since CTA was not diminished when H (10 mg/kg) was injected into rats anesthetised immediately after saccharin drinking by pentobarbital (40 mg/kg), H (1.7–50 μg) was administered intracerebrally to anesthetised rats fixed in the stereotaxic apparatus. Injection of 3–6 μg H into the inferior olive elicited CTA comparable to that of systemic injection of 10 mg/kg H. Injections of 6 and 50 μg H into cerebellum and bulbar reticular formation elicited weaker CTA while neocortical, hypothalamic and mesencephalic applications were ineffective. CTA could also be elicited when 50 μg but not 6 μg H was injected into the inferior olive 1 or 2 h after saccharin drinking. This delay-dependent effect and failure of non-contingent H administration to change saccharin preference indicates that the H-induced CTA is not contaminated by a non-specific increase in neophobia. It is concluded that H probably elicits CTA by activation of caudal bulbar structures, including the nucleus of the solitary tract, area postrema and lateral reticular formation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428552
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  • 27
    Electronic Resource
    Electronic Resource
    Restrained rats learn amphetamine-conditioned locomotion, but not place preference (1984)
    Springer
    Psychopharmacology 84 (1984), S. 163-166 
    Details
    ISSN: 1432-2072
    Keywords: Place-preference ; Amphetamine ; Locomotor behavior ; Conditioned locomotion ; Hyperactivity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The relationship between the motor-activating and positive-reinforcing properties of d-amphetamine was examined in the place-preference paradigm. Two groups of animals were trained to associate one environment with amphetamine, and another environment with saline. Annimals that were allowed to locomote in both environments during training later demonstrated a preference for the amphetamine-paired environment; animals in which hyperactivity was limited in both environments later failed to show any preference. However, both groups of animals demonstrated a conditioned locomotor activation to the amphetamine-associated environments. Our results suggest that a place-preference demonstrated for an amphetamine-paired environment depends on the ability of the drug to increase locomotor behavior.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427440
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  • 28
    Electronic Resource
    Electronic Resource
    Effect of naloxone administration upon responses of adrenal hormones to withdrawal from ethanol (1984)
    Springer
    Psychopharmacology 82 (1984), S. 181-184 
    Details
    ISSN: 1432-2072
    Keywords: Corticosterone ; Adrenal catecholamine ; Ethanol ; Withdrawal ; Naloxone ; Stress ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats maintained on an ethanol-liquid diet developed physical dependence after 16 days. Activation of adrenocortical function and overactivity of the sympathoadrenal system were observed during withdrawal from ethanol. The opiate antagonist naloxone prevented the adrenomedullary response, and attenuated, though not significantly, the increases in serum corticosterone induced by ethanol deprivation. These findings suggest that endogenous opioid pathways may be involved in the ethanol-withdrawal syndrome.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427769
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  • 29
    Electronic Resource
    Electronic Resource
    Involvement of dopamine in the antinociceptive response to footshock (1984)
    Springer
    Psychopharmacology 82 (1984), S. 185-188 
    Details
    ISSN: 1432-2072
    Keywords: Stress ; Antinociception ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of drugs which alter dopaminergic function on footshock-induced antinociception were studied in the rat. Antinociception due to brief (30 s) footshock was inversely related to dopamine (DA). Thus, it was increased by the DA receptor antagonists pimozide and haloperidol and decreased by the specific D2 dopamine receptor agonist LY 141865, but not by the specific D1 agonist SKF 38393. Although pimozide increased the antinociceptive effect of 30-s shock, it decreased that of 30-min shock. It is suggested that DA may have physiological roles in stress-induced antinociception, and that these may differ according to the duration of stress.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427770
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  • 30
    Electronic Resource
    Electronic Resource
    Locomotor hyperactivity caused by dopamine infusion into the nucleus accumbens of rat brain: specificity of action (1984)
    Springer
    Psychopharmacology 82 (1984), S. 174-180 
    Details
    ISSN: 1432-2072
    Keywords: Nucleus accumbens ; Intracerebral infusion ; Dopamine ; Neurotransmitter substances ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats selected as high-activity and low-activity responders to the hyperactivity-inducing action of peripherally administered (-)N-n-propylnorapomorphine [(-)NPA] were subject to intra-accumbens infusion of dopamine, noradrenaline, serotonin, acetylcholine and GABA (0.48 μl/h, 25 μg/24 h, 13 days). Locomotor activity was measured during infusion and for a minimum of 35 days thereafter. After discontinuation of infusion the animals' responsiveness to (-)NPA was also assessed and, on the 2nd day of withdrawal, sensitivity to the hyperactivity-inducing action of acute intra-accumbens dopamine was determined. Dopamine caused a biphasic pattern of hyperactivity during infusion with peaks of responding between days 2–5 and 8–12: normal values returned after withdrawal of infusion. However, 2–3 weeks after withdrawal of intra-accumbens dopamine infusion animals showed reversed responding to (-)NPA challenge, the initial low-active animals giving a high-active response and high-active animals giving low-activity. Infusions of noradrenaline, serotonin, GABA and acetylcholine produced some increase in locomotor activity towards the termination of infusion, but no treatment could replicate the first hyperactivity peak and no treatment, after withdrawal, could reverse the responsiveness to (-)NPA of high- and low-active animals. Acute injections of dopamine into the nucleus accumbens showed that the infusion of the different neurotransmitter substances caused change within that nucleus. Nevertheless, changes in locomotor behaviour following the infusion of dopamine into the nucleus accumbens are specific for dopamine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427768
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  • 31
    Electronic Resource
    Electronic Resource
    Biochemical effects and drug levels in rats after long-term treatment with the specific 5-HT-uptake inhibitor, citalopram (1984)
    Springer
    Psychopharmacology 83 (1984), S. 20-27 
    Details
    ISSN: 1432-2072
    Keywords: Antidepressants ; Citalopram ; Long-term treatment ; Receptor binding ; Beta-receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects in rats of long-term administration of the potent, specific 5-HT uptake inhibitor citalopram have been investigated. Citalopram hydrobromide (MW=405) was given in the diet, 99 or 25 μmol/kg daily, for 13 days or orally, 49 μmol/kg twice a day, for 14 days. High plasma and brain levels of citalopram were found during the treatment period, whereas negligible amounts were found 24 h after withdrawal. The 5-HT uptake mechanism in blood platelets was completely blocked, since levels of whole blood 5-HT during and shortly (2 days) after treatment were decreased by 75–90%. The drug load after the two highest doses in terms of plasma drug levels was the same as in depressed patients treated with citalopram. Receptor binding technique ex vivo was applied to different brain parts to measure receptor parameters for several neurotransmitters. All data were evaluated by Eadie-Hoffstee analysis. No changes were seen in B max and K d for β-receptors (3H-dihydroalprenolol) in frontal cortex, occipital+temporal cortex, whole cortex and limbic structures, 5-HT2 receptors (3H-spiroperidol) in frontal and whole cortex, α1-receptors (3H-prazosin) in “rest of brain” and DA D-2 receptors (3H-spiroperidol) in corpus striatum and limbic structures. The uptake mechanism for 5-HT as well as the inhibitory effect of citalopram on this uptake remained unaffected in brain synaptosomes derived from control and from citalopram (99 μmol/kg)-treated rats. Thus long-term treatment with citalopram does not induce changes in neurotransmitter receptors as seen with most tricyclic as well as newer “atypical” antidepressants. Most striking is the lack of β- and 5-HT2 receptor down-regulation. Since citalopram clinically shows clear antidepressant activity, this down-regulation does not seem to be a prerequisite of antidepressant activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427416
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  • 32
    Electronic Resource
    Electronic Resource
    A note on the rôle of generalized inverse Gaussian distributions of circulatory transit times in pharmacokinetics (1984)
    Springer
    Journal of mathematical biology 20 (1984), S. 95-102 
    Details
    ISSN: 1432-1416
    Keywords: pharmacokinetics ; generalized inverse Gaussian distribution ; recirculatory model ; renewal theory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract Based on a stochastic pharmacokinetical model (which mirrors topological properties of the circulatory system) it is shown by reinterpreting results of Wise (1974) that if the transit times of circulating drug molecules have a generalized inverse Gaussian distribution the corresponding residence times are gamma distributed. The condition that the probability of elimination of a drug molecule in a single circulatory passage is sufficiently small appears to be valid for most drugs. Thus theoretical evidence is given for fitting blood concentration-time curves following bolus injection of a single dose by power functions of time.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00275864
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  • 33
    Electronic Resource
    Electronic Resource
    Interscapular brown adipose tissue blood flow in the rat (1984)
    Springer
    Pflügers Archiv 401 (1984), S. 414-417 
    Details
    ISSN: 1432-2013
    Keywords: Brown adipose tissue ; Microspheres ; Noradrenaline ; Rat ; Regional blood flow ; Xenon clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The xenon clearance method was adapted to continuous measurement of interscapular brown adipose tissue (ISBAT) blood flow in anaesthetized rats. The ISBAT-blood partition coefficient for xenon was determined to 3.6 ml·g−1. The blood flow values obtained by Xe clearance were compared with flow values obtained concomitantly by the microsphere technique in 17 cold acclimated rats, at ISBAT blood flows between 0.1 and 6 ml·g−1·min−1. Variations in blood flows were obtained by infusion of noradrenaline at different rates. The blood flow values obtained from the xenon clearance method showed a close correlation to the blood flow values determined with microspheres.Y=0.98.X+0.15 (r=0.96,P〈0.001). The Xe clearance method has the advantages compared to the microsphere technique that it permits continuous monitoring of the blood flow and does not require the sacrifice of the animal.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00584345
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  • 34
    Electronic Resource
    Electronic Resource
    Drug-induced rhythmic burst activity of cerebellar neurons (1984)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 326 (1984), S. 227-232 
    Details
    ISSN: 1432-1912
    Keywords: Pentobarbital ; Benzodiazepine derivatives ; Cerebellar Purkinje cell ; Interposed nucleus cell ; Discharge pattern ; Rabbit ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The discharge of cerebellar neurons was investigated in the rabbit and the rat under the influence of pentobarbital, diazepam or medazepam. In the rabbit, these drugs are known to induce a rhythm ranging between 4 and 25 Hz in the red nucleus (RN) and the cerebellum (Cb). Purkinje cells (P cells) in the intermediate zone of the cerebellar cortex as well as neurons of the interposed nucleus (IPN) were found to discharge with burst patterns fully synchronized with the drug-induced RN rhythm. In contrast, P cells in the medial cerebellar zone responded to these drugs only with changes in their discharge rate. Since P cells of the intermediate longitudinal zone project to the RN mainly via the IPN, the present findings complement our previous results, indicating that the rhythmic electrical activity in the RN is initiated by the cerebellum. The three drugs had similar effects on the activity of cerebellar units in the rabbit and the rat. The investigation also shows that, in spite of the uniform morphological structure of the cerebellar cortex, P cells do not respond uniformly to a given drug: the diversity of findings published on the P cell response to barbiturates or benzodiazepine derivatives may be explained by differences in the recording sites.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00505323
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  • 35
    Electronic Resource
    Electronic Resource
    Role of muscarinic cholinergic mechanisms in the substantia nigra pars reticulata in mediating muscular rigidity in rats (1984)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 327 (1984), S. 14-17 
    Details
    ISSN: 1432-1912
    Keywords: Bethanechol ; Electromyogram ; Substantia nigra pars reticulata ; Morphine ; Muscular rigidity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Bethanechol chloride (5–25 μg), when injected into the substantia nigra pars reticulata (SNR) of rats, produced muscular rigidity in a dose-dependent way, and in addition, catalepsy and ipsilateral posture. The effects of bethanechol in the dose of 25 μg were prevented by coadministration of 10 μg scopolamine hydrochloride. Injections of 25 μg betanechol or 10 μg scopolamine into the reticulata only slightly affected the muscular rigiditiy produced by 15 mg/kg i.p. morphine hydrochloride. The results suggest that muscarinic cholinergic mechanisms in the substantia nigra pars reticulata, although effective by themselves, affect by expression of at least one striatal functional alteration, the muscular rigidity, in a less effective way than GABAergic or endogenous opioid mechanisms do.
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    URL: http://dx.doi.org/10.1007/BF00504985
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  • 36
    Electronic Resource
    Electronic Resource
    Antinociceptive effects of neonatal capsaicin in rats with adjuvant arthritis (1984)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 326 (1984), S. 248-253 
    Details
    ISSN: 1432-1912
    Keywords: Neonatal capsaicin ; Antinociceptive effects ; Adjuvant arthritis ; Substance P ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats were treated with capsaicin (50 mg/kg, SC) either on the second day or on the second and third days of life. A significant attenuation of the responses to noxious stimuli was obtained in the capsaicin treated animals as measured by the hot-plate or paw pressure tests but not by the tail-flick test. Furthermore, neonatal capsaicin produced a significant reduction of response in the formalin test. Capsaicin reduced the reaction latency in rats with adjuvant arthritis as measured by the hot-plate and paw pressure tests, though capsaicin did not alter the overall time course of the response to Freund's adjuvant. Capsaicin also attenuated the weight loss or the decreased ambulatory and rearing behaviour which occurred in the control animals with adjuvant arthritis. It is suggested that neonatal treatment with capsaicin may relieve the responsiveness to longlasting nociceptive stimuli by adjuvant in rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00505326
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  • 37
    Electronic Resource
    Electronic Resource
    The effect of 2,3-dimercaptopropane sodium sulfonate on mercury retention in rats in relation to age (1984)
    Springer
    Archives of toxicology 55 (1984), S. 250-252 
    Details
    ISSN: 1432-0738
    Keywords: 203Hg ; DMPS ; Age ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effectiveness of DMPS (sodium 2,3-dimercaptopropane-1-sulfonate) in reducing inorganic mercury retention was studied in 2-, 6-, and 28-week-old albino rats. 203Hg was administered IP. The chelating agent DMPS was administered by IP injection at a dose of 250 μmol/kg body weight three times, 1 day after 203Hg administration and at 24 h intervals thereafter. The whole body retention determined 1, 2, 3, and 6 days after 203Hg administration showed that DMPS decreased the body retention of mercury in all age groups, being about twice as effective in adult compared to suckling rats. The reduced effectiveness was due to the reduced efficacy of DMPS in reducing kidney retention in young animals. In other organs the effectiveness of DMPS was not age dependent. These and previous results obtained with different chelating agents and other metals indicate that age might be an important factor in chelation therapy in general.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00341020
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  • 38
    Electronic Resource
    Electronic Resource
    In vivo metabolism of dimethylformamide and relationship to toxicity in the male rat (1984)
    Springer
    Archives of toxicology 56 (1984), S. 87-91 
    Details
    ISSN: 1432-0738
    Keywords: Dimethylformamide ; N-Hydroxymethyl-N-methylformamide ; N-Methylformamide ; Metabolism ; Toxicity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract After in vivo administration of dimethylformamide (DMF) to male rats, about 50% of the dose is excreted in urine as N-hydroxymethyl-N-methylformamide (DMF-OH) and about 4% as N-methylformamide (NMF). NMF is not a product of DMF-OH biotransformation but is directly formed from DMF. Comparison of the acute toxicity of DMF, DMF-OH and NMF shows that NMF is more toxic than DMF-OH, which is itself more toxic than DMF. This study explains the different toxicity profile of DMF and NMF which until recently was believed to represent the main metabolite of DMF.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00349077
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  • 39
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    The toxicity and neuropathology of 2,4,5-tribromoimidazole and its derivatives in rats (1984)
    Springer
    Archives of toxicology 56 (1984), S. 109-112 
    Details
    ISSN: 1432-0738
    Keywords: 2,4,5-Tribromoimidazole ; Rat ; Neuronal necrosis ; Uncoupling of oxidative phosphorylation ; Ataxia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 2,4,5-tribromoimidazole and its 1-n-butylcarboxylate and 1-dimethylcarbamoyl derivatives, when administered to rats, induced poisoning typical of uncouplers of oxidative phosphorylation. At 48 h rats surviving a single toxic dose of 20–60 mg/kg developed permanent incoordination of the hindlimbs in the absence of brain oedema. Neuropathologic examination of brain and spinal cord from perfused fixed rats at 24 h revealed neuronal necrosis and chromatolysis in the vestibular nucleus, the outer parietal neocortex and red nucleus. Chromatolysis and necrosis in these areas had increased at 72–96 h and were also observed in the deeper layers of the neocortex, the medial entorhinal cortex, the reticular formation, the grey matter of the spinal cord extending into the ventral horns, the dorsal, and ventral cochlear nuclei and the deep cerebellar nuclei, in decreasing order of severity. Neuronal necrosis was accompanied by an increased glial response, including neuronophagia and at 16 days with astroglial hypertrophy and hyperplasia.
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    URL: http://dx.doi.org/10.1007/BF00349081
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  • 40
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    Electronic Resource
    Glucuronidation in rat intestinal epithelial cells (1984)
    Springer
    Archives of toxicology 55 (1984), S. 123-126 
    Details
    ISSN: 1432-0738
    Keywords: Rat ; Intestinal cells ; Glucuronidation ; 1-Naphthol ; Glucose ; Fructose ; d-Galactosamine ; Ethanol ; Diethyl ether ; Sorbitol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Glucuronidation of 1-naphthol was studied in mucosal cells isolated from the rat intestine. Glucuronidation was directly dependent on the supply of extracellular carbohydrates. Basal glucuronidation (ca. 0.3 nmoles/min · mg cell protein) was increased 2- to 3-fold by adding glucose or fructose to the incubation medium. Saturation of glucuroniation was achieved by adding 0.3 mM glucose, while saturation by fructose was not reached at concentrations below 2 mM. No carbohydrate reserves able to support glucuronidation appear to be present in intestinal cells, since no difference in glucuronidation was observed between cells prepared from fasted (18 or 42 h) and control rats. Glucuronidation was decreased by adding d-galactosamine to the incubation medium, but only when extracellular glucose was present. Various chemicals which are known to inhibit glucuronidation in hepatocytes (ethanol, diethyl ether, sorbitol) did not influence the glucuronidation of 1-naphthol in isolated intestinal cells. Only when ethanol was added to mucosal cells in the absence of extracellular glucose was a small decrease in glucuronidation observed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00346050
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  • 41
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    Electronic Resource
    Phthalate esters (1984)
    Springer
    Archives of toxicology 55 (1984), S. 132-136 
    Details
    ISSN: 1432-0738
    Keywords: Phthalate esters ; Inhalation ; Rat ; Enzymatic activities
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male Sprague Dawley rats were exposed to dibutylphthalate (DBP) by inhalation with concentrations of 0.5, 2.5, and 7.0 ppm in the air for 5 days. The concentrations were considered relevant to human exposure. No quantitative changes were observed in liver microsomal cytochrome P-450 related enzymes, but significant increase was observed in the liver microsomal metabolism of benzo(a)pyrene and n-hexane, in the 2.5 ppm and 0.5 ppm groups, respectively. Inhaled DBF decreased in a dose-dependent way the lung microsomal concentration of cytochrome P-450 by as much as 63%, which was reflected in a significant reduction of the microsomal metabolism of n-hexane and benzo(a)pyrene in the 7.0 ppm group. It is concluded that DBP in doses relevant to human air exposure influences the cytochrome P-450 enzyme system in both liver and lung, with lung as the main target organ. The observed effects in lung microsomes were similar to those earlier reported after IP administration of high doses of DBP.
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    URL: http://dx.doi.org/10.1007/BF00346052
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  • 42
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    A method of studying the intestinal absorption of aluminium in the rat (1984)
    Springer
    Archives of toxicology 55 (1984), S. 168-172 
    Details
    ISSN: 1432-0738
    Keywords: Aluminium ; Intestinal absorption ; Methodology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aluminium (Al) intoxication in dialysis patients is held to be caused not only by Al in the dialysis fluid but also by Al from orally administered phosphate binders. Studies on Al absorption in patients and healthy individuals as well as in animals are still scarce, and do not provide sufficient data to characterize the absorption process. This paper presents a method of studying the process of Al absorption in a perfusion system of rat small intestine in vivo, in combination with a cannulation system of the portal vein for serial blood sampling. Determination of concentrations of an absorbed substance in samples of both the perfusion medium and the portal blood, collected during the perfusion period, may clarify the nature of the absorption process. Although this method appears to be useful for the study of the intestinal absorption of any substance, it was adapted for the study of the intestinal absorption of Al compounds. The usefulness of this method for studying Al absorption was demonstrated in an experiment in which Al chloride (0.5 g/l) in buffered media of pH 7.0, 7.5, and 8.0 was perfused through the rat small intestine over a period of at least 30 min. The results of this experiment indicate that a decrease in pH of the perfusion medium leads to an increase in absorption of Al in the portal blood.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00316122
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  • 43
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    Electronic Resource
    Do prostaglandins mediate the somatostatin preventive effect on gastric lesion? (1984)
    Springer
    Cellular and molecular life sciences 40 (1984), S. 974-975 
    Details
    ISSN: 1420-9071
    Keywords: Rat ; prostaglandins ; gastric lesion ; intragastric distension model ; stress model ; indomethacin ; somatostatin preventive effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The inhibition of endogenous prostaglandin synthesis by indomethacin treatment blocks the somatostatin preventive effect on the gastric lesions induced in a stress model and has no preventive effect on an intragastric distension model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01946466
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  • 44
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    Electronic Resource
    Corticotropin releasing factor increases the adrenocortical responsiveness to adrenocorticotropin (1984)
    Springer
    Cellular and molecular life sciences 40 (1984), S. 1004-1006 
    Details
    ISSN: 1420-9071
    Keywords: Rat ; adrenocortical responsiveness ; ACTH ; plasma ; corticosterone ; plasma ; corticotropin releasing factor (CRF)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In the course of studying the plasma adrenocorticotropic hormone (ACTH) and corticosterone responses to synthetic corticotropin releasing factor (CRF), we noted some disparity in the responses. A higher dose (20 μg compared with 5 μg per rat i.a.) produced an equal plasma ACTH but greater plasma corticosterone response in adult male rats. Thus, we examined the possibility that CRF increases adrenocortical responsiveness to ACTH. CRF significantly (p〈0.0005) increased the plasma corticosterone response to ACTH in rats pretreated with dexamethasone. Thus, synthetic CRF increases corticosterone secretion in rats not only by stimulating ACTH secretion, but also by increasing the adrenocortical responsiveness to ACTH.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01946481
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  • 45
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    Electronic Resource
    Intracerebroventricular injection of cerebrospinal fluid (CSF) from a patient with congenital indifference to pain induces analgesia in rats (1984)
    Springer
    Cellular and molecular life sciences 40 (1984), S. 1365-1366 
    Details
    ISSN: 1420-9071
    Keywords: Rat ; cerebrospinal fluid, human ; analgesia ; naloxone ; pain indifference, congenital ; opiates, endogenous
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary CSF from a patient with congential indifference to pain was found to produce analgesia in the rat following intracerebroventricular injections. The analgesic effect was attenuated by pretreatment with naloxone suggesting the involvement of hyperactive endogenous opiate mechanisms in this patient.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01951891
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  • 46
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    Electronic Resource
    15-Hydroxyprostaglandin dehydrogenase and hexokinase in spontaneously hypertensive rat kidney (1984)
    Springer
    Cellular and molecular life sciences 40 (1984), S. 1368-1369 
    Details
    ISSN: 1420-9071
    Keywords: Rat ; kidney ; hypertensive ; prostaglandin dehydrogenase ; hexokinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary 15-Hydroxyprostaglandin dehydrogenase (PGDH) surged in hypertensive (SHR) and normotensive (WKY) rat kidney at 8 days of age, is greatest in SHR. Hexokinase fell in SHR at 17 days of age, but thereafter was similar to WKY. This suggests multisystem enzymatic abnormalities in SHR kidney during development of hypertension.
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    URL: http://dx.doi.org/10.1007/BF01951893
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  • 47
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    Electronic Resource
    Ethanol preference in rats with a prior history of acetaldehyde self-administration (1984)
    Springer
    Cellular and molecular life sciences 40 (1984), S. 1008-1010 
    Details
    ISSN: 1420-9071
    Keywords: Rat ; ethanol preference ; acetaldehyde self-administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Peripherally self-injected acetaldehyde in interaction with environmental and nutritional variables significantly enhances alcohol drinking in rats and suggests an involvement of acetaldehyde in voluntary alcohol intake.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01946483
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  • 48
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    The splenius capitis muscle of the rat, architecture and histochemistry, afferent and efferent innervation as compared with that of the quadriceps muscle (1984)
    Springer
    Anatomy and embryology 169 (1984), S. 79-89 
    Details
    ISSN: 1432-0568
    Keywords: Splenius muscle ; Muscle fiber types ; Primary afferents ; Spinal cord ; Brain stem ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The splenius muscle of the rat was investigated with regard to its structure and innervation. The latter was compared with that of the quadriceps muscle. The results can be summarized as follows: The splenius muscles of both sides form a bipennate muscle plate connecting the occipital bone with the spinous process of the second thoracic vertebra. The lateral parts of both muscles are attached directly to this prominent bony process, whereas the medial parts end in a median raphe which forms a tendinous cranial extension of the second thoracic vertebra. This tendinous extension, showing no connection to the cervical vertebrae, serves also for the attachment of acromio-trapezius muscle fibers. The lateral part of the splenius muscle is divided into two parts by a tendinous intersection. The splenius muscle consists mainly of fast twitch fibers: 55% were characterized as IIB and 40% as IIA fibers by histochemical demonstration of myosin ATPase-activity. A high content of muscle spindles — 57 spindles per gram of muscle tissue — was found. Comparing several aspects of the innervation of the splenius to that of the quadriceps muscle, the following results could be obtained: 1. The ratio of motor end plate size to muscle fiber volume is significantly higher in the splenius than in the quadriceps muscle. 2. As demonstrated by transganglionary HRP-transport, the main part of labeled splenius afferents to the spinal cord terminates in the central cervical nucleus. Quadriceps afferents, entering the lower thoracic and upper lumbar segments, mainly end in the area of Clarke's column. Several labeled fibers descend to the sixth lumbar and first sacral segments, where they terminate in the area of Stilling's nucleus. 3. A group of primary afferents from both muscles-most probably III- and IV-afferents — projects to the dorsal laminae of the dorsal horn; terminals from the splenius are accumulated in the lateral parts of these laminae, where-us those of the quadriceps are more concentrated in the medial areas. 4. Within the brain stem, most afferents from the splemus terminate in the external cuneate nucleus. Most of the quadriceps afferents course to the gracile nucleus. 5. Terminals from both muscle nerves were found in the area of the spinal vestibular nucleus. In conclusion, the most conspicuous results were: 1) Besides the segmental projection to the dorsal horn there is an almost exclusive projection of splenius primary afferents to relay nuclei to the cerebellum. 2) The relatively high ratio: end plate size/muscle fiber volume, which is characteristics of finely adjusting muscles. These results provide additional clues to the understanding of the particular role of the neck muscles in posture and head movement.
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    URL: http://dx.doi.org/10.1007/BF00300589
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    Morphometric studies of the extraglomerular mesangial cell field in volume expanded and volume depleted rats (1984)
    Springer
    Anatomy and embryology 170 (1984), S. 217-222 
    Details
    ISSN: 1432-0568
    Keywords: Juxtaglomerular apparatus ; Extraglomerular mesangial cell field ; Structure-function correlation ; Resetting of tubuloglomerular feedback ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The extraglomerular mesangial cell field was studied by morphometric techniques in volume expanded and volume depleted rats. The volume density of the extraglomerular mesangial interstitium was found to be significantly different between the two conditions, 16.9±3.7% in volume depletion and 29.0±4.1% in volume expansion. No difference in the volume density of the peritubular interstitium could be detected under the same conditions. These findings are interpreted as indicating a specific sensitivity of the extraglomerular mesangial interstitium to changes in body fluid content, a phenomenon which may play a role in the mechanism of resetting the tubulo-glomerular feedback control.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00319007
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  • 50
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    An immunohistochemical study of somatostatin and neurotensin positive neurons in the septal nuclei of the rat brain (1984)
    Springer
    Anatomy and embryology 170 (1984), S. 1-10 
    Details
    ISSN: 1432-0568
    Keywords: Somatostatin ; Neurotensin ; Immunohistochemistry ; Septum ; Basal forebrain ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Antibodies to the neuropeptides somatostatin (SOM) and neurotensin were used to study the distribution of the two peptides within the septum of the rat brain. In colchicine treated rats, numerous somatostatin-positive cell bodies were found in the dorsal and ventral subdivisions of the alteral septum, along the border of the nucleus accumbens, in the ventral tip of the horizontal limb of the diagonal band of Broca as well as in the anterior hippocampal rudiment, infralimbic area and several other structures of the basal forebrain (e.g., nucleus accumbens, olfactory tubercle and substantia innominata). Cell bodies containing immunoreactivity for neurotensin were situated in the intermediate and ventral subdivisions of the lateral septum, the medial septal nucleus, the diagonal band of Broca, the rostro-medial continuation of the substantia innominata and the olfactory tubercle. In untreated rats, somatostatin positive processes formed terminal plexuses in the medial septal nucleus and along an area close to the ventricular wall of the lateral ceptal nucleus. Other septal nuclei, such as the diagonal band of Broca contained a sparse innervation by somatostatin positive fibers. In contrast, the nucleus accumbens olfactory tubercle, and the substantia innominata contained a rich innervation by somatostatin positive axons and terminals. Within these structures the density of SOM positive processes show great variations with patches of densely packed terminals separated by areas of sparser or no innervation. The neurotensin positive terminals were situated predominantly within the intermediate part of the lateral septum and the medial septal nucleus. Both of these regions contained numerous pericellular baskets of neurotensin positive terminals around septal neurons. In addition to the septal innervation, several of the basal forebrain structures were rich in neurotensin positive processes with the densest innervation found in the nucleus accumbens and substantia innominata. Like the SOM-immunoreactivity distinct islands of dense neurotensin innervation separated by less or no innervation occur throughout the basal forebrain. Taken together, these findings suggest that somatostatin and neurotensin occur in separate neuronal populations and that each may influence important physiological functions within the individual septal nuclei.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00319452
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    Electronic Resource
    Pericytes on the dermal microvasculature of the rat skin (1984)
    Springer
    Anatomy and embryology 169 (1984), S. 271-274 
    Details
    ISSN: 1432-0568
    Keywords: Scanning electron microscopy ; Pericyte ; Skin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Surface morphology of pericytes of the subepidermal capillary network of rat skin was studied by scanning electron microscopy. Pericytes showed considerable variation in shape, one end of the spectrum representing a fusiform cell body and lateral projections, the other end a club-like, undulated appearance. Most cells of whatever form were disposed parallel to the capillary course and aligned on the dermal side of the vessels. The pericytic processes encompassed up to half of the endothelial circumference, and were not tapered but spatulated at the ends; the cells adhered to the vessel wall only in certain areas. These findings, together with our previous observation that the subepidermal capillaries exhibit fenestrations mainly at the epidermal side of the endothelial lining, suggest a possible functional role of the pericyte in control of material exchange through the vessel wall. The lateral processes of the fusiform pericytes may, by contraction, cause thinning of the capillary endothelium and the formation of fenestrae, while the club-like pericytes may straighten and push the capillary towards the epidermis, if pericytes are indeed contractile cells, as recent studies indicate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315632
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  • 52
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    Effects of dorsal rhizotomy on the several types of primary afferent terminals in laminae I–III of the rat spinal cord (1984)
    Springer
    Anatomy and embryology 170 (1984), S. 279-287 
    Details
    ISSN: 1432-0568
    Keywords: Terminal degeneration ; Dorsal rhizotomy ; Glomeruli ; Spinal cord ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary After cervical dorsal rhizotomy, small dark central terminals (CI) of glomeruli underwent electron dense changes at 8 h and were all degenerated at 36 h; their number persisted, though slightly diminished, up to 15 days, glial engulfment being negligible. Light large central terminals without neurofilaments (CIIa) showed electron-lucent or electron-dense degeneration from 14 to 36 h, while those with neurofilaments (CIIb) exhibited increased neurofilamentous areas, with depletion and presynaptic concentration of synaptic vesicles as in the electron-lucent change, at the 8–36 h postrhizotomy periods. Both CII-varieties were all degenerated at 36 h and became electron dense at 48 h; glial phagocytosis was intense and no terminals were present after 4 days. It is concluded that in the rat the 3 types of central glomerular terminals are primary axons, and that each type undergoes a different pattern of degeneration which points to a separate primary afferent origin. Numerous nonglomerular axodendritic endings began showing electron-dense degeneration at 8 h which rapidly masked their normal structure, although most appeared to contain round agranular vesicles, and some of them dense-cored vesicles (in lamina I). A few endings exhibited electronlucent degeneration. Labeling methods seem preferable for studying the primary origin of nonglomerular terminals, due to the difficulty in recognizing the normal predegenerative structure of these profiles.
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    URL: http://dx.doi.org/10.1007/BF00318731
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    The perineuronal net in the fastigial nucleus of the rat cerebellum (1984)
    Springer
    Anatomy and embryology 170 (1984), S. 79-85 
    Details
    ISSN: 1432-0568
    Keywords: Perineuronal net ; Astrocytes ; Fastigial nucleus ; Cerebellum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The morphological study of the rat fastigial nucleus with the Golgi-Rio Hortega method showed the presence of glial perineuronal nets surrounding the large neurons, but not the small ones. This perineuronal net appeared as a mesh of tenuous glial processes which covers the neuronal perikarya and proximal dendrites. The small alveolate compartments in this mesh seem to correspond to the holes for the synaptic boutons. Our results also indicate that the perineuronal net is derived from interneuronal protoplasmic and velate astrocytes. Using camera lucida drawings of this perineuronal net we have made a quantitative estimation of the size and density of synaptic boutons on these large neurons. The average numerical density of synaptic boutons was about 19 per 100 μm2 of the neuronal surface, the mean area of the synaptic holes being 2.5 μm2. Furthermore, the quantitative data evidence that about 52.5% of the neuronal surface is presumably occupied by synaptic boutons whereas the remaining 47.5% is covered by the glial processes of the perineuronal net. Semithin sections prepared from thick Golgi sections were used for the cytological study of the neurons surrounded by this glial pericellular network. The possible functional significance of the perineuronal net in the regulation of synaptic transmission in the fastigial cerebellar nucleus is briefly discussed.
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    URL: http://dx.doi.org/10.1007/BF00319461
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  • 54
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    Sexual differences in the topographical distribution of serotonergic fibers in the anterior column of rat lumbar spinal cord (1984)
    Springer
    Anatomy and embryology 170 (1984), S. 117-121 
    Details
    ISSN: 1432-0568
    Keywords: Sexual dimorphism ; Serotonin fibers ; Lumbar cord ; Cremaster ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sexual dimorphism in the topographical organization of immunoreactive serotonergic fibers has been shown for the first time in the anterior column of the rat lumbar cord. A characteristic preferential arrangement of serotonergic fibers on the small cell column composed of anterior horn motoneurons, which have been proved to send their axons to the cremaster muscle, was demonstrated at the lumbar segments (L1–L2) of male rats, using the immunoperoxidase technique with antiserum against serotonin. A similar finding was also observed in female rats, but was less prominent than in males. Comparative analysis of the cell numbers and the size of neuronal somata of the aforementioned nucleus, done using retrograde transport of fluorescent dye (DAPI) via axonal fibers coursing down the genitofemoral nerve to the cremaster muscle, gave significantly larger values in males. The sexual difference in the serotonergic innervation pattern was, in consequence, surmised to be caused by the cytoarchitectonic contrast ascertained in the lumbar anterior column. Furthermore, there may be a striated muscle endowed with some active functions homologous to those of the male cremaster muscle in the female rat.
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    URL: http://dx.doi.org/10.1007/BF00318995
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  • 55
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    Adrenal interference of insulin secretion after 14-days oestradiol treatment in female rats (1984)
    Springer
    Diabetologia 26 (1984), S. 76-80 
    Details
    ISSN: 1432-0428
    Keywords: Rat ; islets of Langerhans ; oestradiol treatment ; adrenal glands ; corticosterone treatment ; insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ovarian-adrenal interactions on insulin secretion during oestradiol treatment were studied in sham-operated, ovariectomized and adrenalectomized-ovariectomized female rats, the latter thus treated to suppress interference from endogenous hormones. Islets of Langerhans isolated from oestradiol or oestradiol + corticosterone treated and control rats were incubated with various glucose concentrations. Oestradiol treatment enhanced basal and glucose stimulated insulin secretion from sham-operated (+12%) or ovariectomized rats (+24%). This effect disappeared in adrenalectomized-ovariectomized rats but reappeared when adrenalectomized-ovariectomized rats were treated with oestradiol + corticosterone (+37%). A 14-day oestradiol treatment had a trophic effect on total protein content independent of adrenal presence (+14%; +15%; +31%; +23% versus respective control groups). Our data demonstrate that corticosterone is necessary for the stimulating effect of oestradiol on insulin secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00252268
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  • 56
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    Study of porcine and human isophane (NPH) insulins in normal subjects (1984)
    Springer
    Diabetologia 26 (1984), S. 261-265 
    Details
    ISSN: 1432-0428
    Keywords: Porcine NPH insulin ; semi-synthetic and biosynthetic human NPH insulin ; pharmacokinetics ; pharmacodynamics ; normal subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The plasma glucose, C-peptide and insulin responses to subcutaneously administered highly purified porcine, ‘semi-synthetic’ and ‘biosynthetic’ human isophane (NPH) insulin and diluting medium as control in normal male subjects were evaluated. Porcine and semi-synthetic human NPH insulins were administered at two dose levels of 0.15 and 0.30 U/kg body weight and biosynthetic human NPH at 0.15 U/kg body weight only. At the low dose level the three insulin preparations resulted in a similar maximal hypoglycaemic effect within 3–5 h after administration. However, over the remainder of the 11 h post-injection period, the plasma glucose level was lower after semi-synthetic human insulin. In contrast, at the 0.30 U/kg dose level, there was no difference in the early or late hypoglycaemic response between porcine and semi-synthetic human NPH insulins of equivalent pharmaceutical formulation. The clinical relevance of these findings needs further evaluation. The data suggest that for the ‘intermediate-acting’ NPH insulin preparations, both the species of insulin, nature and quantity of the retarding protein and their subsequent interaction may determine their time-action characteristics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00283647
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  • 57
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    Dietary protein: a trigger of insulin-dependent diabetes in the BB rat? (1984)
    Springer
    Diabetologia 26 (1984), S. 297-299 
    Details
    ISSN: 1432-0428
    Keywords: Rat ; pathogenesis ; insulin-dependent diabetes ; dietary proteins ; milk proteins ; wheat proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Animals from a colony of spontaneously diabetic insulin-dependent BB rats were fed from weaning with semisynthetic diets in which natural proteins were replaced by l-amino acids with or without the addition of either milk or wheat proteins. The normal 50% incidence of diabetes in the colony was reduced to 15% in rats fed the basic semi-synthetic diet, while it was 35% and 52% when supplemented with gluten or milk, respectively. Thus, dietary factors might precipitate the expression of the disease.
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    URL: http://dx.doi.org/10.1007/BF00283653
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  • 58
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    Electronic Resource
    Tubular lesions in streptozotocin-diabetic rats (1984)
    Springer
    Diabetologia 27 (1984), S. 32-37 
    Details
    ISSN: 1432-0428
    Keywords: Rat ; kidney ; streptozotocin diabetes ; tubular lesions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Renal tubular lesions have been studied in streptozotocin-diabetic rats after 50 days of diabetes and compared with age-matched controls. The kidney weight increased by 67% in the diabetic animals and the length of the proximal tubules increased by 22%, but no abnormalities were found. The length of the distal tubules increased by 20% and the total increase was due to abnormal distal tubules. These abnormalities were confined to the cortex and the outer stripe of the outer medulla, but they were not seen in the inner stripe of the outer medulla. Abnormal cells were found also in the distal tubular cells of the macula densa. The total length of the collecting ducts was the same in the two groups and the cells appeared normal. The cells of the abnormal distal tubules appeared either empty or full of a PAS-positive material, digestable with α-amylase. At the electron microscope level, the cytoplasm of the cells contained glycogen-like granules, strikingly few organelles and the basal infoldings were greatly reduced. It is suggested that these tubular lesions might play a role in the development of renal functional changes in diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00253498
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  • 59
    Electronic Resource
    Electronic Resource
    Effects of dithiobiuret intoxication on motor end plates in sternocostalis and hindlimb muscles of female rats (1984)
    Springer
    Acta neuropathologica 65 (1984), S. 77-84 
    Details
    ISSN: 1432-0533
    Keywords: 2,4-dithiobiuret ; Rat ; Motor end plate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Daily dosing with 1–3 mg/kg dithiobiuret for 4–5 days causes progressive, generalised muscle weakness which is fatal in about 50% of cases on day 4 or 5. Survivors recover mobility by day 7 and appear normal, although still weak. Striking changes in the motor nerves and motor end plates can be observed before and during the development of this weakness, using the zinc iodide-osmium staining technique. The terminal internodes of intramuscular axons become densely stained: later this may extend back into the main intramuscular (i.m.) nerves, and is often followed by axonal degeneration. Many motor end plates lose their branching form and become globular, and profuse terminal sprouting develops before any nerve degeneration appears. Following axonal degeneration, collateral sprouting becomes prominent, and, within four weeks of beginning the dose regime, restores the normal appearance of the innervation. This pattern of response was observed clearly in the whole mounts of the sternocostalis muscle: similar but less marked changes occurred in the lumbrical muscles, while in the soleus and tibialis anterior muscles, loss of end plates seemed to be a more common response. Despite marked differences in the severity of the functional disability, the i.m. changes were similar in juvenile and adult rats. These changes are related to previous electrophysiological findings on the possible mechanism of action of dithiobiuret.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689831
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  • 60
    Electronic Resource
    Electronic Resource
    The density and distribution of ischemic brain injury in the rat following 2–10 min of forebrain ischemia (1984)
    Springer
    Acta neuropathologica 64 (1984), S. 319-332 
    Details
    ISSN: 1432-0533
    Keywords: Cerebral ischemia ; Selective vulnerability ; Neuronal necrosis ; Cell death ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The density and distribution of brain damage after 2–10 min of cerebral ischemia was studied in the rat. Ischemia was produced by a combination of carotid clamping and hypotension, followed by 1 week recovery. The brains were perfusion-fixed with formaldehyde, embedded in paraffin, subserially sectioned, and stained with acid fuchsin/cresyl violet. The number of necrotic neurons in the cerebral cortex, hippocampus, and caudate nucleus was assessed by direct visual counting. Somewhat unexpectedly, mild brain damage was observed in some animals already after 2 min, and more consistently after 4 min of ischemia. This damage affected CA4 and CA1 pyramids in the hippocampus, and neurons in the subiculum. Necrosis of neocortical cells began to appear after 4 min and CA3 hippocampal damage after 6 min of ischemia, while neurons in the caudoputamen were affected first after 8–10 min. Selective neuronal necrosis of the cerebral cortex worsened into infarction after higher doses of insult. Damage was worst over the superolateral convexity of the hemisphere, in the middle laminae of the cerebral cortex. The caudate nucleus showed geographically demarcated zones of selective neuronal necrosis, damage to neurons in the dorsolateral portion showing an all-or-none pattern. Other structures involved included the amygdaloid, the thalamic reticular nucleus, the septal nuclei, the pars reticularis of the substantia nigra, and the cerebellar vermis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00690397
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  • 61
    Electronic Resource
    Electronic Resource
    Assessment of drug metabolism in hepatic disease: Comparison of plasma kinetics of oral cyclobarbital and the intravenous aminopyrine breath test (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 95-101 
    Details
    ISSN: 1432-1041
    Keywords: cyclobarbital ; aminopyrine ; liver disease ; 14CO2 breath test ; barbiturate ; pharmacokinetics ; hepatic drug metabolism ; cirrhosis ; alcoholic liver disease ; viral hepatitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The exhalation of 14CO2 derived from an i.v. tracer dose of [dimethylamine-14C]aminopyrine has been investigated in normal controls and patients. They subsequently ingested 200 mg cyclobarbital calcium in the evening and the decline in the plasma drug level over the following 2 days was measured by thin-layer chromatography. The peak specific activity of exhaled 14CO2 occurred 0.5–2 h after 14C-aminopyrine injection in the absence of liver disease and in non-cirrhotic liver disorders. It was delayed in certain patients with cirrhosis. Compared to 8 medically healthy subjects, 10 patients with acute viral hepatitis, 8 with cirrhosis and 10 with fatty liver exhibited a significantly increased half-life of 14CO2 exhalation. Normal mean values were found in 12 patients with non-cirrhotic alcoholic liver disease and in 14 patients with non-hepatic diseases. The cyclobarbital (CB) half-life was prolonged and the clearance reduced in patients with viral hepatitis, cirrhosis, or alcoholic liver damage as compared to data from 17 control subjects. Due to a larger apparent volume of distribution, patients with fatty liver disease had an increased CB half-life, although its clearance was normal. A close negative correlation was detected between the clearance and the logarithm of the CB level measured 36 h after drug ingestion. The oral CB test evaluated from a single blood sample taken about 36 h after drug administration appears to be a useful indicator of human drug metabolising capacity. Discrimination between patients with and without disordered liver function was similar in the two drug elimination tests.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00546715
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  • 62
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of midazolam in the aged (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 381-388 
    Details
    ISSN: 1432-1041
    Keywords: midazolam ; hypnotic drug ; benzodiazepine ; pharmacokinetics ; aged patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of midazolam, an imidazo-benzodiazepine derivative, have been studied in 13 subjects over the age of 60 years who received the drug intravenously (0.07 mg kg−1) as an induction agent for endoscopy. Two to three days later, 6 of these subjects received 5 mg of midazolam intramuscularly, and another 6 of the subjects received 10 mg of the drug orally. The plasma concentration-time curves were again studied pharmacokinetically. After intravenous dosing, the mean (± SD) elimination half-life (2.14±1.24 h) showed a statistically significant trend to increase with age in the subjects older than 60 years. While the mean (± SD) clearance value (0.30±0.19 l kg−1h−1) tended to fall with age in the elderly subjects, this trend was not statistically significant. Apparent volume of distribution did not appear to be related to advancing age beyond 60 years, and this parameter (mean ± SD) did not differ to a statistically significant extent between the aged subjects (0.77±0.47 l kg−1) and the young subjects studied previously (1.09±0.58 l kg−1). Atropine premedication did not appear to alter the dispositional parameters of the intravenously administered drug. Intramuscularly administered midazolam was absorbed rapidly. Bioavailability appeared incomplete (F=0.59±0.15, mean ± SD), possibly due to saturable elimination of the drug at the higher plasma levels which were obtained after intravenous midazolam. Oral bioavailability, relative to intravenous, was 0.34±0.17, (mean ± SD), with an appreciable but variable lag time (0.74±0.40 h, mean ± SD). Orally, in the dose used, the drug was an inefficient hypnotic with four of the six subjects failing to attain the plasma drug level of 44–50 µg l−1, which appeared to be the approximate threshold for sleep. It is impossible to know whether this failure represents an age related effect on drug absorption, or is a consequence of the upper alimentary tract abnormalities for which the endoscopies were done.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00548771
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  • 63
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    Electronic Resource
    Single and multiple dose kinetics of clobazam, and clinical effects during multiple dosage (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 499-503 
    Details
    ISSN: 1432-1041
    Keywords: benzodiazepines ; clobazam ; desmethylclobazam ; pharmacokinetics ; sedation ; accumulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen healthy volunteers, aged 19 to 62 years, took a single 20-mg oral dose of clobazam and the serum concentrations of clobazam and desmethylclobazam were measured for the following 7 days. The mean kinetic variables for clobazam were: volume of distribution 1.31/kg, elimination half-life 24 h, total clearance 0.47 ml/min/kg. 13 of the volunteers then took clobazam 5 mg twice daily for 22 consecutive days. Serum concentrations were measured during and after this period. Both clobazam and desmethylclobazam showed slow and extensive accumulation, their steady-state kinetics being entirely consistent with those observed after single doses. Elimination of both compounds after termination of treatment was equally slow. Clinical self-rating of morning sedation indicated a significant increase over baseline in subjective perception of sedation during the treatment period, and this effect persisted into the washout period. However, sedation did not increase in parallel with accumulating levels of clobazam and desmethylclobazam, probably due to functional adaptation or tolerance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542148
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  • 64
    Electronic Resource
    Electronic Resource
    Bioequivalence studies in humans of indomethacin capsules marketed in India (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 261-264 
    Details
    ISSN: 1432-1041
    Keywords: indomethacin capsules ; bioequivalence ; volunteers ; pharmacokinetics ; statistical significance ; bioavailability ; comparative bioequivalence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Two, separate 6×6 Latin square cross-over bioequivalence studies were performed in adult male volunteers using 10 different indomethacin capsule preparations marketed in India together with the pure drug powder as the standard. The products were evaluated with respect to plasma level at various times up to 8 h following administration of a 50 mg (2 × 25 mg) dose. Plasma samples were analysed by a fluorimetric method. Various pharmacokinetic parameters were calculated according to a two compartment model. Statistical evaluation of the data employed analysis of variance for a cross-over design (ANOVA) and Duncan's multiple range test to ascertain the significance of differences between the products. Of the 10 products studied, two were found to be bioinequivalent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00630296
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  • 65
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    Electronic Resource
    Pharmacokinetics of cefoxitin administered by i.v. infusion to patients with a pleural effusion (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 389-392 
    Details
    ISSN: 1432-1041
    Keywords: cefoxitin ; beta-lactam antibiotics ; pharmacokinetics ; serum concentration ; pleural fluid concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cefoxitin was studied in 6 healthy volunteers and in 5 patients with a pleural effusion after administration of a single dose of 30 mg/kg i.v. infusion. The serum and pleural fluid concentrations of cefoxitin were determined microbiologically. The elimination half-life of the antibiotic from pleural fluid in all cases was 2–3fold longer than from serum, which shows a difference between the kinetic elimination processes of the antibiotic from the two fluids. The slow elimination of cefoxitin from pleural fluid facilitates its accumulation in this compartment during a multiple dosage regimen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00548772
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  • 66
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    Electronic Resource
    Acetaminophen accumulation in pediatric patients after repeated therapeutic doses (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 57-59 
    Details
    ISSN: 1432-1041
    Keywords: acetaminophen ; pediatric patients ; fever therapy ; accumulation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acetaminophen serum concentrations were studied in 21 infants and children with fever. The maximum serum concentrations ranged from 9.96 to 19.6 µg/ml after a single dose of 12–14 mg/kg and 13.9 to 40.1 µg/ml after a single dose of 22–27 mg/kg. Ten patients were restudied at steadystate after repeat doses had been given every 4 or 8 h for 1 to 3 days. Total area under the acetaminophen serum concentration-time curve normalized for dose averaged 0.181 (ml/min/kg)−1 after the first dose and 0.202 (ml/min/kg)−1 at steady-state (p〈0.05). Five patients showed a 13 to 44% increase in the AUC; one had a 10% decrease in the AUC; and four had less than 6% change in the AUC. There was no evidence of hepatotoxicity. These data suggest that acetaminophen may accumulate after repeated therapeutic doses in children with fever.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00553155
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  • 67
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    Electronic Resource
    Pharmacokinetics of canrenone and metabolites after base hydrolysis following single and multiple dose oral administration of spironolactone (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 441-446 
    Details
    ISSN: 1432-1041
    Keywords: spironolactone ; canrenone ; metabolites ; pharmacokinetics ; single/multiple oral doses ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of canrenone and ‘total metabolites’ after base hydrolysis was studied in eight young volunteers following single and multiple dose oral administration of spironolactone. The plasma levels of canrenone and ‘total metabolites’ were fitted to a two-compartment open model with a first-order absorption process. From our eight normal subjects studied, the harmonic mean of the distributive half-life (t1/2α) of canrenone was found to be 1.66 h, and the harmonic mean of the terminal elimination half-life (t1/2β) to be 22.6 h. Harmonic means of the distributive and elimination half-lives of ‘total metabolites’ after base hydrolysis were 2.48 h and 28.8 h respectively. The accumulation ratio of canrenone was 2.53, whereas that of ‘total metabolites’ was 1.89. Despite the fact that spironolactone has been shown to induce hepatic metabolism of other drugs, no evidence of autoinduction was noted in the present study, as plasma levels of canrenone and ‘total metabolites’ were found to obey a linear two-compartment model with reproducible absorption and disposition after single and multiple doses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00549592
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  • 68
    Electronic Resource
    Electronic Resource
    A “once a day administration” sustained-release theophylline formulation: Disposition and pharmacokinetics (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 325-328 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; sustained release ; pharmacokinetics ; chronic administration ; healthy volunteers ; plasma levels ; GCMS assay ; stable isotope technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a new sustained-release preparation of theophylline (Dilatrane à Action Prolongée capsules filled with homogenous microgranules) has been after its studied administration to 7 healthy volunteers at 8 p.m. in order to achieve therapeutic levels at night and in the morning. In separate trials the test dose of 500 or 600 mg was administered for 7 days, once daily at 8 p.m. Plasma theophylline levels were measured by capillary gas chromatography with a mass specific detector after pentylation, using internal standards labelled with stable isotopes (15N-1,3 and 13C-2 theophylline). The new sustained-release preparation showed a monophasic regular absorption phase with very low interindividual variability. After administration, the plasma level stayed within 80% of the peak levels for 8.5±1.5 h. There was a good correlation between the dose and the steady state plasma level (r=0.9587; p〈0.05). This preparation can be chronically administered once daily day at 8 p.m. in order to achieve a therapeutic level during the night and the morning, and to provide sufficient protection during the nycterohemeral period, with a once dose a day schedule.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542169
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  • 69
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of a fixed combination of sotalol and hydrochlorothiazide in hypertensive patients with moderate renal insufficiency (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 361-362 
    Details
    ISSN: 1432-1041
    Keywords: sotalol ; hydrochlorothiazide ; pharmacokinetics ; moderate renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Decreased elimination of a combined formulation of Sotalol (160 mg) and hydrochlorothiazide (25 mg) was found in patients with moderate renal insufficiency. Very slight accumulation of sotalol and hydrochlorothiazide was observed, so it appears unnecessary to reduce the dosage in patients with a creatinine clearance of 30 ml/min or more.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542176
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  • 70
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    Electronic Resource
    The pharmacokinetics of a new radiosensitiser, Ro 03-8799 in humans (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 483-489 
    Details
    ISSN: 1432-1041
    Keywords: radiosensitiser ; pharmacokinetics ; healthy volunteers ; tumour patients ; Ro 03-8799
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A new hypoxic cell radiosensitiser, Ro 03-8799 has been administered intravenously to human volunteers and its kinetic parameters derived from plasma and urine data. Good penetration of drug into tumour tissue is found, consistent with its large volume of distribution. The plasma clearance of this compound is rapid due to high metabolic and renal clearances. These parameters combine to produce an elimination half-life of 5.6 h, approximately half that of misonidazole, a well studied radiosensitiser. It is hoped that this decrease in total body exposure will also reduce the cumulative toxicity seen when misonidazole is administered repeatedly.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00549599
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  • 71
    Electronic Resource
    Electronic Resource
    Inter- and intra-subject variation in the first-pass elimination of highly cleared drugs during chronic dosing (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 47-53 
    Details
    ISSN: 1432-1041
    Keywords: verapamil ; first-pass metabolism ; pharmacokinetics ; interindividual variation ; intraindividual variation ; chronic administration ; deuterated verapamil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of verapamil in five healthy volunteers were investigated on 4 occasions during chronic administration of deuterated verapamil. There was no statistically significant difference in oral clearance, terminal half-life, bioavailability, morning trough level and peak concentration or in the time of their occurrence on the four occasions. The plasma clearance, however, exhibited considerable inter- and intra-individual variation, ranging between 26.3% and 85.4% and 12.0% and 48.0%, respectively. Comparison of these pharmacokinetic parameters with data from previous single dose studies in the same subjects revealed a significant (p〈0.05) decrease in the clearance and an increase in the apparent bioavailability of verapamil during chronic administration, although no difference in the half-life was found. Due to the considerable variation in the oral clearance of verapamil during chronic dosing, steady-state conditions in a strict pharmacokinetic sense may never be attained, and pharmacokinetic data obtained in single dose studies will be of limited value in predicting steady-state plasma concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00546708
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  • 72
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    Electronic Resource
    Pharmacokinetic evaluation of haemoperfusion in phenobarbital poisoning (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 109-112 
    Details
    ISSN: 1432-1041
    Keywords: phenobarbital poisoning ; charcoal haemoperfusion ; distribution volume ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Charcoal haemoperfusion was performed for 5–12 h in three patients with maximal plasma phenobarbital concentrations of 600, 946 and 1044 µmol/l (138, 217 and 240 µg/ml). During haemoperfusion with constant blood flow phenobarbital elimination followed first order kinetics with half-lives of 11.1, 10.0 and 7.2 h, respectively. After termination of the haemoperfusion there was no rebound effect in plasma phenobarbital concentration and the elimination was first order with half-lives of 51, 82 and 48 h, respectively. Thus, the plasma phenobarbital half-life was reduced by 78–88% during haemoperfusion. In the same period 76–86% of the total body clearance of phenobarbital was due to the haemoperfusion column at a calculated volume of distribution of phenobarbital of 1.1–1.2 l/kg. This is clear evidence for recommending haemoperfusion in cases of serious poisoning with phenobarbital.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00546717
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  • 73
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    Electronic Resource
    Pharmacokinetics of nadolol in healthy subjects (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 125-127 
    Details
    ISSN: 1432-1041
    Keywords: nadolol ; pharmacokinetics ; plasma levels ; urinary excretion ; bioavailability ; circadian rhythm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 7 healthy subjects (3 males and 4 females), the kinetics of nadolol was investigated after oral doses of 60 and 120 mg. The t1/2 was 14.0±1.8 h. The peak plasma level was doubled on doubling the dose (from 69±15 to 132±27 ng/ml, respectively) and the urinary excretion (13.5%) rose similarly. The half-life of elimination was longer at night than in the day, probably because of the slower nocturnal flow of urine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00546720
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  • 74
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    Electronic Resource
    Pharmacokinetics of furosemide in man after intravenous and oral administration. Application of moment analysis (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 197-207 
    Details
    ISSN: 1432-1041
    Keywords: furosemide ; bioavailability ; pharmacokinetics ; oral administration ; i.v. administration ; drug absorption ; moment analysis ; food effect ; dissolution effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Furosemide 40 mg was administered to 8 healthy subjects as an i.v. bolus dose, as 1 tablet in the fasting state, and as 1 tablet and a solution after food intake. The i.v. data gave a total body clearance of 162±10.8 ml/min and a renal clearance of 117±11.3 ml/min; the volume of distribution at steady state was 8.3±0.61. Oral administration gave a bioavailability of the tablet (fasting) of 51%. Food intake slightly reduced the bioavailability, but not to a significant extent. There was no significant difference in availability between the tablet and the solution. Moment analysis gave a mean residence time after the i.v. dose, MRTi.v., of 51±1.5 min. The mean absorption times (MAT) for all oral doses were significantly longer than the MRTi.v., indicating absorption rate-limited kinetics of furosemide. On average, food delayed the absorption by 60 min. The MAT for the tablet in the postprandial state was significantly longer than for the solution, indicating dissolution rate-limited absorption of the tablet.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00630286
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  • 75
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    Electronic Resource
    Pharmacokinetics of epidural morphine in man (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 233-237 
    Details
    ISSN: 1432-1041
    Keywords: morphine ; anesthesiology ; epidural application ; pharmacokinetics ; plasma level ; CSF level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cerebrospinal fluid (CSF) and plasma morphine concentrations were determined in 5 patients after epidural administration of 6 mg morphine; plasma samples were collected frequently during the initial 6 h and 6–7 CSF samples were obtained from each patient over a 24 h period. Morphine was analysed using gas chromatography and electron capture detection. Individual morphine concentration-time curves were plotted for plasma and CSF and various pharmacokinetic variables were calculated. Plasma morphine concentrations after epidural injection were similar to those found after intramuscular administration; Cmax (66±8 mg/ml: mean±SEM) appeared within 12±3 min, and the terminal elimination half-life in plasma was 213±24 min. In CSF, morphine reached a peak (1575±359 ng/ml) after 135±40 min. The terminal elimination half-life for morphine in CSF was 239±10 min. The CSF bioavailability of morphine after epidural administration was calculated to be 1.9±0.5%. The study showed that epidural administration of morphine resulted in CSF concentrations many times higher than those in plasma, but still only 2% of the dose administered was available to the CSF compartment. Morphine was eliminated with similar speed from CSF and plasma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00630291
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  • 76
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    Electronic Resource
    Pharmacokinetic and pharmacodynamic modelling with pancuronium (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 243-250 
    Details
    ISSN: 1432-1041
    Keywords: pancuronium ; neuromuscular relaxants ; simultaneous modelling ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and pharmacodynamics of pancuronium were studied following intravenous infusion in eleven patients undergoing surgical anaesthesia. Measurement of the plasma concentrations (Cp) of the neuromuscular blocking agent (NMBA) and the concomitant intensities of paralysis allowed their simultaneous modelling. The pharmacokinetic parameters derived for pancuronium were in the range of previously reported values, except that the mean total systemic plasma clearance (0.79±0.28 ml·min−1·kg−1) was reduced and the mean terminal phase half-life (169 min) was longer in these patients. Plasma concentration and % paralysis data were successfully fitted to a previously proposed pharmacodynamic model. This model assumes a separate effect compartment which exchanges drug directly with the central kinetic compartment (integrated effect model). The ‘steady-state’ Cp necessary to produce 50% paralysis (ECpss(50)) was estimated to be 0.21±0.08 µg·ml−1 (mechanical response) and 0.18±0.05 µg·ml−1 (EMG response). An analysis using the Hill equation of the Cp-response relationship, during and after the constantrate infusion of pancuronium bromide, resulted in effective plasma concentrations for 50% paralysis (ECp50) of 0.35±0.06 µg·ml−1 and 0.20±0.09 µg·ml−1, respectively, for mechanical twitch response. The corresponding values for EMG response were 0.32±0.06 µg·ml−1 and 0.17±0.06 µg·ml−1. Using this latter approach, the ECp50 estimated during onset of paralysis was significantly higher than that estimated during offset of paralysis (p〈0.05); no such difference was apparent between this latter parameter and the ECpss(50) of the integrated effect model (p〉0.05). No significant differences were observed between any of the pharmacodynamic parameter estimates generated from the data obtained from the two methods of assessment of neuromuscular function (mechanical vs. EMG response) (p〉0.05).
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    URL: http://dx.doi.org/10.1007/BF00630293
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  • 77
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    Electronic Resource
    Effect of aluminium phosphate on the bioavailability of cimetidine and prednisolone (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 271-273 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; prednisolone ; aluminium phosphate ; antacids ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten fasting subjects received 200 mg cimetidine orally either with water or 11 g aluminium phosphate mixture in a randomized, single dose, two-way cross-over study. Blood samples were taken for 12 h and urine was collected for 24 h. Cimetidine in plasma and urine was analysed by HPLC. There were no significant differences between the treatments with respect to peak plasma concentration, time to peak plasma concentration, area under the plasma concentration-time curve, and urinary excretion. In 12 healthy subjects the absorption of prednisolone was investigated when given alone and together with 11 g aluminium phosphate. Blood samples were taken over 16 h and prednisolone in plasma was analysed by HPLC. There were no significant differences in the values of area under curve (AUC), Cmax and tmax. The results indicate that aluminium phosphate does not reduce the bioavailability of cimetidine and prednisolone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00630299
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  • 78
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    Electronic Resource
    Pharmacokinetics of cimetidine in advanced cirrhosis (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 347-355 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; cirrhosis ; pharmacokinetics ; bioavailability ; clearance reduction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of impaired liver function on the pharmacokinetics of cimetidine was studied in 8 patients with advanced cirrhosis given single doses of 100 mg i.v. and 400 mg p.o. on separate days. Compared to a control group of 10 healthy volunteers, the total renal and nonrenal clearance was significantly reduced in the cirrhotic patients; (total plasma clearance mean ± SD) 356±181 vs 789±262 ml/min (p〈0.01); renal clearance (Clr) 296±100 vs 588±181 ml/min (p〈0.01) and nonrenal clearance (Clnr) 97±111 vs 205±89 ml/min (p〈0.05). Compared to published results for age-matched ulcer patients, both total and nonrenal clearance were lower whereas renal clearance was within the reported normal range. A significant reduction in volume of distribution (Vdβ) was found, from 2.1±0.1 l/kg in controls to 1.0±0.4l/kg, and in the patient group there was a significant correlation between Vdβ and total plasma clearance (r=0.72, p〈0.05). Volume of distribution in steady state (Vdss) did not differ from published results in age-matched controls. No significant change in half-life was found. Bioavailability, estimated by AUC-measurement, showed considerable patient variability (21–143%), with a mean of 70±39%. This was lower than in the controls. In contrast, measurement of urinary excretion showed higher bioavailability in the patients (66±23 vs 51±8%). No correlation was found between any of the kinetic parameters and the clinical and laboratory data. It is suggested that patients with advanced cirrhosis should be closely observed when given cimetidine, and a reduction in dose should be concidered if side effects are to be avoided.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00548766
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  • 79
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    Electronic Resource
    Steady state pharmacokinetics of trimethoprim 300 mg once daily in healthy volunteers assessed by two independent methods (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 393-397 
    Details
    ISSN: 1432-1041
    Keywords: trimethoprim ; concentration ; urinary excretion ; healthy volunteers ; steady state ; pharmacokinetics ; serum creatinine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The steady state pharmacokinetics of trimethoprim was determined after 300 mg orally once daily to 6 healty volunteers for 9 days. The microbiological assay of plasma level was unreliable at trimethoprim concentrations 〉4 µg/ml, so results from an HPLC-assay are given. Steady state was present after 3 days. The plasma concentration peaked 1 to 4 h (mean 2.0 h) after the dose at a mean of 6.0 µg/ml (range 3.1–9.5 µg/ml); the minimum value was 1.5 µg/ml (range 0.6–2.9 µg/ml). The mean AUCss was 77 µg/ml · h and the mean plasma clearancess was 67 and 74 ml/min on Days 8 and 9. Renal clearance was about 60% of the plasma clearance. The average plasma half life was 10.6 h (range 8.7–15.3 h). Thus, there was considerable interindividual variation in all pharmacokinetic parameters. 72 h after the last dose trimethoprim was detectable in plasma in only 1 of the 6 subjects. The minimum urinary concentration of trimethoprim during treatment was always well above (range 22 to 220 µg/ml) the MIC values for most urinary tract pathogens. Therefore, a daily dose of 300 mg trimethoprim results in a therapeutic concentration in urine at steady state that lasts throughout the dosing interval and in most subjects probably lasts also for a further 24 h. Trimethoprim administration raised mean serum creatinine from 67 to 97 µmol/l, probably due to competitive inhibition of the tubular secretion of creatinine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00548773
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  • 80
    Electronic Resource
    Electronic Resource
    Comparison of the short-term effects of the loop diuretic piretanide and furosemide in patients with renal insufficiency (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 413-418 
    Details
    ISSN: 1432-1041
    Keywords: piretanide ; furosemide ; renal insufficiency ; loop diuretic ; natriuresis ; pharmacokinetics ; diuretic effect ; kaliuresis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The natriuretic effect of the new loop diuretic piretanide was investigated in patients with severe renal insufficiency and was compared with that of furosemide. In the first study 4 hospitalized patients (serum creatinine 407 to 1220 µmol/l) were examined after administration of piretanide (12, 24, 48 and 96 mg to two patients, and 24, 48, 96 and 192 mg to 2 other subjects, given every third day). In the second study 6 hospitalized patients (serum creatinine 194 to 698 µmol/l) were studied after receiving orally 2 different doses of piretanide and 2 different doses of furosemide orally, given every fourth day. The mean natriuretic effect of 48 mg and 96 mg piretanide was 250 and 340% of the control value for the entire group, and 311 to 480% in the subgroup of patients with serum creatinine below 530 µmol/l. For a given dose the natriuresis was inversely correlated with renal function, and at a given serum creatinine level the natriuretic response was dose-dependent. The drug had less effect on water and potassium diuresis than on natriuresis. No significant difference in natriuretic effect was found on comparison with furosemide given in the ratio furosemide: piretanide 3.33:1. The pharmacokinetic data showed a direct correlation between the dose and the mean plasma concentration and also between urinary recovery of the drug and the measured natriuretic response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542133
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  • 81
    Electronic Resource
    Electronic Resource
    Individualizing theophylline dosage: Evaluation of a single-point maintenance dose prediction method (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 491-498 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; computer simulation ; pharmacokinetics ; single-point dose prediction ; nomogram
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A dosage prediction method to estimate theophylline clearance and dose requirement was evaluated in 22 outpatients with partly reversible obstructive airways disease. The steady state theophylline dose required to achieve a target concentration (Css) was predicted using a single serum theophylline determination 8 h after a single oral test dose. In 17 nonsmoking patients a mean absolute deviation of 8.2% (range 0.0–21.7%) between predicted and observed Css was found, and in 5 smoking patients the mean deviation was 34.0% (range 2.2–53.8%). In 17 healthy smokers the single-point method was found to predict theophylline clearance at a sampling time of 8 h with a prediction error of 11.3 (range 0.8–25.3%) compared to the clearance determination using the area under the curve. In addition, a numerical simulation program to assess the influence of absorption, elimination and sampling time on predictive accuracy showed that the method could be successfully applied to a patient population with elimination rate constants between 0.07 1/h and 0.25 1/h, allowing a mean prediction error of 15%.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542147
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  • 82
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    Electronic Resource
    Comparison of radioreceptor assay and radioimmunoassay for atropine: Pharmacokinetic application (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 613-617 
    Details
    ISSN: 1432-1041
    Keywords: atropine ; radioreceptor assay ; radioimmunoassay ; serum levels ; pharmacokinetics ; assay comparison
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A membrane suspension prepared from rat brain was able to bind the potent muscarinic antagonist quinuclidinyl benzilate (QNB). The KD for binding was 0.48 nM and Bmax was 1.42 pmol/mg protein. Atropine competitively inhibited the binding of tritiated QNB to muscarinic receptors. This new radioreceptor assay (RRA) for atropine has been compared with a radioimmunoassay (RIA) for atropine. The RRA measures only the active component of atropine, 1-hyscyamine and in this respect it differs from the RIA. As little atropine as 1.25 ng/ml (4.33 nmol/l) in a 25 µl serum sample could be reliably assayed by the RRA. Using both assay techniques the pharmacokinetics of atropine was studied after a single 0.02 mg/kg i.v. dose given to 8 anaesthetized patients. The half-life calculated by the RRA was 3.7±2.3 h (m ± SD) and by the RIA 4.3±1.7 h. Both the volume of distribution and the total clearance were higher according to the RRA than the RIA: 3.9±1.5 vs 1.7±0.71/kg and 15.4±10.3 vs 5.9±3.6 ml/min/kg, respectively. The AUC measured by the RRA and RIA was 29.8±18.9 and 103.9±110.7 µg·h/l, respectively. The differences in the pharmacokinetics according to the 2 methods are presumably due to preferential tissue uptake of the l-form.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543495
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  • 83
    Electronic Resource
    Electronic Resource
    Oral pharmacokinetics of omeprazole (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 641-643 
    Details
    ISSN: 1432-1041
    Keywords: omeprazole ; gastric acid secretion ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of omeprazole were studied in a group of healthy male subjects after single and repeated oral doses of 30 and 60 mg. Absorption of omeprazole from its enteric-coated formulation was unpredictable. There was a highly significant increase in the area under the plasma concentration time curve (AUC) after repeated dosing. Omeprazole increases its own relative availability following repeated dosing. This may be due to inhibition of gastric acid secretion by omeprazole which is an acid-labile compound.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543502
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  • 84
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    Electronic Resource
    Bioavailability and pharmacokinetics of phenytoin during pregnancy (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 105-110 
    Details
    ISSN: 1432-1041
    Keywords: phenytoin ; epileptic women ; pharmacokinetics ; bioavailability ; pregnancy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five epileptic women needing to commence phenytoin therapy during pregnancy received a single intravenous and a single oral dose of phenytoin several days apart before starting regular intake of the drug. Plasma phenytoin concentration — time data were analysed by three different pharmacokinetic techniques. However assessed, the mean oral bioavailability of the drug proved to be about 90% of the intravenous bioavailability. This finding makes it unlikely that impaired bioavailability accounts for the increase in oral phenytoin dosage necessary in pregnancy to maintain plasma phenytoin concentrations at pre-pregnancy values. Phenytoin clearance in the pregnant subjects was approximately double the published values for phenytoin clearance in nonpregnant persons. This suggests that increased (metabolic) clearance accounts for the increased phenytoin dosage requirement of pregnancy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00553163
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  • 85
    Electronic Resource
    Electronic Resource
    Effect of food on pharmacokinetics of chlorambucil and its main metabolite, phenylacetic acid mustard (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 111-114 
    Details
    ISSN: 1432-1041
    Keywords: chlorambucil ; chronic lymphocytic leukaemia ; phenylacetic acid mustard ; food intake ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of food intake on the pharmacokinetics of chlorambucil (C) and its cytotoxic metabolite, phenylacetic acid mustard (PAM), has been studied in man after oral doses of chlorambucil. The administration of chlorambucil with food resulted in slower absorption than when fasting. However, the area under the plasma concentration-time curve (AUC) was unaffected. The mean ratio AUCPAM/AUCC was 2.8 (range 1.4–7.1) under fasting and 3.3 (range 1.3–7.4) under nonfasting conditions. The metabolite very probably plays an important role in the cytotoxic effects observed after administration of C, since calculations show that a major fraction of the metabolite is eliminated by alkylation reactions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02395216
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  • 86
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    Electronic Resource
    Pharmacokinetics of S-adenosyl-L-methionine in healthy volunteers (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 119-121 
    Details
    ISSN: 1432-1041
    Keywords: S-adenosyl-L-methionine ; pharmacokinetics ; protein binding ; dose-dependent kinetics ; healthy volunteers ; urinary excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary S-Adenosyl-L-methionine (AdoMet) kinetics was studied in 6 male subjects given 100 and 500 mg i. v. Drug concentrations in plasma and urine were assayed using a radioenzymatic method. Pharmacokinetic parameters were estimated according to an open two-compartment model. The apparent volumes of distribution after the 100 and 500 mg doses were 407±27 and 443±36 ml/kg (mean±SEM), terminal half-lives 81±8 and 101±7 min and body clearances 3.7±0.5 and 3.1±0.2 ml/min per kg. Urinary excretion was 34±3 and 40±2% of the administered dose. The results demonstrate that drug disposition occurs more via metabolism than via renal excretion, and it is not dependent on the administered dose. Binding of AdoMet to serum proteins is negligible.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02395218
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  • 87
    Electronic Resource
    Electronic Resource
    Papaverine disposition in cardiac surgery patients and the effect of cardiopulmonary bypass (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 127-130 
    Details
    ISSN: 1432-1041
    Keywords: papaverine ; cardiopulmonary bypass ; pharmacokinetics ; cardiac surgery patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cardiac surgery involving cardiopulmonary bypass (CPB) causes substantial physiologic changes which may potentially alter the pharmacokinetic properties of drugs used during and after the procedure. Studies with fentanyl have implied a relationship between prolonged elimination half-lives following CPB and decreased liver perfusion during and after the procedure. To further test this hypothesis, the effects of CPB on the pharmacokinetics of papaverine, a coronary vasodilator currently being added to the cardioplegic solution to prevent vasospasm, were studied. The drug was given to two groups of patients, one (n=6) undergoing surgery with and one (n=5) without CPB, the latter serving as controls. Plasma papaverine concentrations declined biexponentially in the control patients with a mean elimination half-life of 1.30±0.25 h, total plasma clearance of 13.8±3.75 ml/min/kg, volume of distribution of 1.52±0.45 l/kg and volume of distribution, steady-state, of 0.992±0.530 l/kg. For the CPB group, only half-life was estimated, and averaged 2.77±0.28 h, significantly greater (p〈0.01) than that in the controls. These results further confirm the increased half-lives seen with other hepatically cleared drugs following CPB and have implications in the clinical management of patients given drugs eliminated in this manner.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544033
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  • 88
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of meptazinol after single and multiple oral administration to elderly patients (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 223-226 
    Details
    ISSN: 1432-1041
    Keywords: meptazinol ; pharmacokinetics ; multiple dosing ; elderly patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Oral administration of meptazinol (200 mg Meptid®) to male and female geriatric patients (〉70 years) resulted in rapid absorption, with peak drug concentrations at 0.5 to 3 h after dosage. Subsequent elimination also proceeded rapidly with a half-life of 3.39 h (±0.26 SEM) after a single dose and 4.97 h (±0.80 SEM) after 13 consecutive 6-h doses. These values were not statistically different. There was no accumulation of meptazinol above that expected from the single-dose kinetics. Plasma protein binding of meptazinol was 33.8% (±0.74 SEM). No sex difference was apparent in any of the pharmacokinetic parameters determined. Comparison of these results with those obtained in an earlier study in young volunteers showed that although the half-life of meptazinol was somewhat longer than the value of 2 h seen in the young, peak plasma concentrations after single and multiple dosing were similar for both age groups, implying that clearance remained largely unaltered. It was concluded that there was no pharmacokinetic basis for recommending a reduction in dosage when treating elderly patients with oral meptazinol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544049
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  • 89
    Electronic Resource
    Electronic Resource
    Identification of a prazosin metabolite and some preliminary data on its kinetics in hypertensive patients (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 275-280 
    Details
    ISSN: 1432-1041
    Keywords: prazosin ; hypertensive patients ; prazosin metabolite ; HPLC assay ; pharmacokinetics ; hypotensive effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A metabolite of prazosin was detected in serum from hypertensive patients treated with prazosin. Its structure as 2-(1-piperazinyl)-4-amino-6,7-dimethoxyquinazoline was established by UV, IR, and mass-spectrometry. An assay method for simultaneous determination of prazosin and its metabolite in serum, urine and saliva is described. Preliminary data about the kinetics of prazosin and the metabolite after a single oral dose of prazosin 1 mg, and after multiple doses of 1 to 5 mg t.i.d. for 6–82 days in 7 patients with hypertension, are presented. After the single dose the metabolite level was much lower than that of intact drug, even though the former was eliminated much more slowly than the latter. The slow elimination of the metabolite led to its eventual accumulation in serum during multiple administration. The mean accumulation ratio of the metabolite was estimated to be at least 5.5 (from 3.0 to 7.9). Prazosin itself had a low accumulation ratio, so the mean steady-state level of the intact drug on multiple administration was several times lower than that of metabolite. As this metabolite has some hypotensive effect in animals, it may account for part of the therapeutic activity of parzosin in patients. The mean steady-state concentration of intact prazosin during the course of treatment were found to be significantly lower than that predicted from a single dose study.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542159
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  • 90
    Electronic Resource
    Electronic Resource
    Effect of cimetidine and ranitidine on carbamazepine and sodium valproate pharmacokinetics (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 341-343 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; ranitidine ; carbamazepine ; sodium valproate ; pharmacokinetics ; drug metabolism ; inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a single oral dose (400 mg) of carbamazepine and sodium valproate were compared in peptic ulcer patients before and after four weeks of a therapeutic course of either cimetidine (1 g/day, n=6 subjects) or ranitidine (300 mg/day, n=6 subjects). There was a small (up to 20%) but statistically significant decrease in oral clearance of carbamazepine after cimetidine treatment. A similar fall in sodium valproate clearance in five cimetidine-treated patients was accompanied by a significantly prolonged elimination half-life. No such trends were demonstrated during ranitidine treatment. Since both anticonvulsants are partly metabolized by hepatic mixed function oxidases, an inhibition by cimetidine at this level may be responsible for the observed impairment of clearance. Thus a potentially important clinical interaction may occur in patients taking anticonvulsants and cimetidine concurrently.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542172
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  • 91
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and pharmacodynamics of a novel orally active angiotensin converting enzyme inhibitor (HOE 498) in healthy subjects (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 577-581 
    Details
    ISSN: 1432-1041
    Keywords: HOE 498 ; ACE inhibitor ; pharmacokinetics ; pharmacodynamics ; urinary excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and pharmacodynamics of the angiotensin converting enzyme inhibitor HOE 498 were investigated in 10 healthy normotensive male subjects. Serum levels of the active metabolite M 1 (dicarboxylic acid) of HOE 498 were measured by HPLC up to 14 days after a single oral dose of 10 m g HOE 498. Peak serum concentration of M 1 between 5–50 ng/ml was observed 1.5–3.0 h after administration. The serum concentration-time curve of M 1 was polyphasic and exhibited a prolonged terminal phase with a half-life of approximately 110 h. Despite the long terminal half-life M 1 could not be detected in urine later than 72 h after administration. The activity of the angiotensin converting enzyme in plasma was completely suppressed for up to 12 h, and 72 h after dosing 50% inhibition of the enzyme was still observed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00556895
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  • 92
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    Electronic Resource
    Pharmacokinetic and pharmacodynamic interaction study of diazepam and metoprolol (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 223-226 
    Details
    ISSN: 1432-1041
    Keywords: diazepam ; metoprolol ; drug combination ; pharmacodynamics ; pharmacokinetics ; drug metabolism ; sedation ; interaction study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 6 normotensive, healthy male volunteers the pharmacodynamic responses (blood pressure, heart rate; sedation index, tracking test, reaction time) to metoprolol (100 mg bid orally), diazepam (0.1 mg/kg intravenously) and to their combination were studied. The pharmacokinetics of diazepam were also compared in a cross-over experiment, with and without pretreatment by the β-adrenoceptor antagonist to evaluate the possibility of a drug interaction. The pharmacodynamic and pharmacokinetic investigations indicated that metoprolol only slightly impaired the elimination of diazepam (18% decrease in total clearance, 25% increase in elimination half-life). The pharmacodynamics of metoprolol (17% decrease in heart rate, 17% decrease in diastolic RR) was not significantly altered by the bolus injection of diazepam. The extent of prolongation in choice reaction time (RT2) induced by diazepam was significantly (p=0.001) more pronounced following the co-administration of metoprolol. However, the results of RT1, the tracking test and the sedation index did not indicate any increased effect due to the β-blocking agent. It is concluded that concomitant treatment with metoprolol and diazepam causes only minor and clinically irrelevant changes in drug metabolism and drug response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00630289
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  • 93
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    Electronic Resource
    Comparative pharmacokinetics of sulphasalazine and sulphapyridine after rectal and oral administration to patients with ulcerative colitis (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 275-277 
    Details
    ISSN: 1432-1041
    Keywords: sulphapyridine ; sulphasalazine ; pharmacokinetics ; rectal administration ; oral administration ; plasma levels ; ulcerative colitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Rectal administration of sulphasalazine to patients with ulcerative colitis has recently been shown to have similar therapeutic activity but fewer side effects than oral treatment. The present study is a comparison of the pharmacokinetics of sulphasalazine (SASP) and its metabolite sulphapyridine (SP) after rectal and oral administration of SASP to 6 patients with ulcerative colitis. The areas under the concentration-time curves (AUC) and the maximum concentrations (Cmax) of SASP and SP were significantly lower after rectal than oral administration of SASP (p〈0.05). These findings support the view that the lower frequency of side effects after rectal administration of SASP may result from the lower plasma levels of SASP and SP.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00630300
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  • 94
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    Electronic Resource
    Relationship between the cardiovascular effects and steady-state kinetics of clonidine in hypertension (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 309-313 
    Details
    ISSN: 1432-1041
    Keywords: clonidine ; hypertension ; therapeutic window ; steady state concentration ; pharmacokinetics ; cardiovascular effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Clonidine was given orally as monotherapy in increasing daily doses from 3.1 to 25.7 µg/kg to patients with essential hypertension (n=6). When a steady state concentration in plasma was reached at each dose level, the blood pressure (BP) and heart rate were measured during a dosage interval. Effect time — plasma concentration data were submitted to nonlinear regression analysis, which showed that the observed BP effects could be dissociated into depressor and pressor components. A window for the antihypertensive effect was established. At a plasma clonidine concentration of 0.65±0.07 ng/ml 50% of the maximal depressor effect was found, and it was only separated by a factor of 2 from the half maximal pure pressor concentration in plasma. No relationship between the change in heart rate and the plasma clonidine was observed. The findings strengthen the importance of close monitoring of clonidine therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00548760
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  • 95
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    Electronic Resource
    Pharmacokinetics and pharmacodynamics of transdermally administered clonidine (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 79-85 
    Details
    ISSN: 1432-1041
    Keywords: clonidine ; transdermal application ; pharmacodynamic effect ; pharmacokinetics ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Clonidine was applied to the skin of healthy volunteers once weekly by means of a Transdermal Therapeutic System (TTS). The plasma concentration and renal excretion of clonidine, and its effects on mean arterial blood pressure (MAP) and heart rate (HR) were recorded for 7 days, followed by a three-day observation period when a second TTS was applied. Subjective side effects were semiquantitatively recorded. Four differents TTS formulations were tested; of which TTS-RP 600679 was the most effective. Following application of this formulation, the plasma level of the drug built-up up during the first 2 days and then remained stable for 120 h at therapeutic concentrations between 0.5 and 0.7 ng/ml; MAP was consistently reduced. During the steady state period the daily urinary clonidine excretion was in the same range as during chronic administration of Catapres tablets 0.15 mg every 12 h, or Catapres Perlongets 0.25 mg every 24 h. Transdermal clonidine applications renewed weekly provide the following therapeutic advantages: 1. patients are protected continuously throughout the entire steady state period; 2. daily fluctuations in plasma clonidine concentration are minimized, which may result in a marked reduction in side effects; and, 3. drug compliance should be improved.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00546713
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  • 96
    Electronic Resource
    Electronic Resource
    Effect of a reversible and selective MAO-A inhibitor (cimoxatone) on diurnal variation in plasma prolactin level in man (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 71-77 
    Details
    ISSN: 1432-1041
    Keywords: cimotaxone ; MAO inhibitor ; plasma prolactin ; circadian rhythm ; healthy volunteers ; hypothalamic MAO ; prolactin secretion ; metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prolactin (PRL) secretion is stimulated by serotonin (5-HT) and inhibited by dopamine (DA). 5-HT is generally recognized as a substrate for type A monoamine oxidase (MAO), whereas DA is considered as a substrate for either A or B, or both forms of MAO, depending on the species and tissues used. The effect of cimoxatone, a reversible, selective MAO-A inhibitor, on diurnal variation in plasma PRL level was investigated in healthy adults after a single 40 mg oral dose, as an indirect approach to investigating whether DA is preferentially a substrate for Type A or B MAO in man. The circadian rhythm in PRL, stress conditions and diet were taken into account in the present study, which was placebo-controlled. There was a slight but significant reduction in circulating PRL in the six subjects, which persisted for at least 9 h after cimoxatone. However, the duration of the decrease in plasma PRL was shorter than the inhibition of MAO-A. The results are not inconsistent with the presence of both forms of MAO in the human hypothalamus and with DA as a substrate for both forms in this region, if it is assumed that the hypothalamic concentrations of the drug during the period 0–9 hours was sufficiently high to inhibit DA deamination by both forms of MAO.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00546712
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  • 97
    Electronic Resource
    Electronic Resource
    Correlation between the pharmacokinetics and pharmacodynamics of dopamine in healthy subjects (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 163-169 
    Details
    ISSN: 1432-1041
    Keywords: dopamine ; pharmacokinetics ; pharmacodynamics ; adrenaline plasma level ; noradrenaline plasma level ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and the pharmacodynamic action of dopamine were investigated in 5 healthy subjects. Dopamine was given in different doses (200, 400 and 800 µg/min) by constant intravenous infusion over 90 min. In order to control the influence of the procedure on the measured parameters the subjects also received a similar infusion of saline. Dopamine, noradrenaline and adrenaline levels in plasma were followed for up to 6 h after the infusion, and arterial pressure and heart rate were monitored. Dopamine reached a steady state level within 15 to 30 min after commencement of the infusion; the steady state levels averaged 36.5 µg/l at 200 µg/min, 73.8 µg/l at 400 µg/min and 207 µg/l at 800 µg/min. The corresponding total clearances were 5.8 l/ min, 5.51/min and 3.9 l/min suggesting non-linear kinetics. The kinetics could not be described by compartmental model. Noradrenaline and adrenaline levels were found to be elevated during infusion of dopamine. Noradrenaline had returned to its pretreatment level within 15 to 30 min after cessation of the infusion, whereas the adrenaline level did not return to the pretreatment value within the observation period. Heart rate was increased by the dose of 400 µg/min, and the systolic and mean arterial pressures were elevated, whereas distolic blood pressure remained unchanged. Elevated systolic blood pressure was better correlated with plasma dopamine than with noradrenaline concentration. This finding, in conjunction with the unchanged diastolic blood pressure, indicates that elevation of the systolic blood pressure is a direct rather than an indirect effect of dopamine. The increased heart rate was not correlated with the dopamine level.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00630281
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  • 98
    Electronic Resource
    Electronic Resource
    Intrapatient variation in tobramycin kinetics in low birth weight infants during first postnatal week (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 647-649 
    Details
    ISSN: 1432-1041
    Keywords: tobramycin ; newborn infants ; intrapatient variations ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nineteen newborn infants receiving tobramycin, 2.5 mg/kg every 12 h were studied on two occasions at steady-state during the first week of postnatal age. The two studies were separated by two to four days. Total body clearance of tobramycin averaged 1.15 and 1.14 ml/min/kg (p〉0.05), apparent volume of distribution averaged 0.82 and 0.68 l/kg (p〉0.05), and elimination half-life averaged 8.6 and 7.1 h (p〉0.05), during the first and second study, respectively. When the data were further analyzed based on the birth weight, tobramycin kinetics changed during the second study compared to the first study in very low birth weight infants. In eight infants ⩽1.5 kg birth weight, although total clearance of tobramycin was similar, the average apparent volume of distribution decreased from 1.04 l/kg during the first study to 0.73 l/kg during the second study (p〈0.05) and elimination half-life from 11.1 h during the first study to 8.7 h during the second study (p〈0.05). These data indicate that these infants may require a change in dosing interval with continued tobramycin therapy during the first week of postnatal age. Intrapatient variation in tobramycin kinetics should be considered, in addition to the interpatient variation reported previously, when monitoring the serum concentration to individualize tobramycin therapy in newborn infants ⩽1.5 kg birth weight.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543504
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  • 99
    Electronic Resource
    Electronic Resource
    D-propoxyphene kinetics in man: Significance of a deep third compartment (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 749-752 
    Details
    ISSN: 1432-1041
    Keywords: dextropropoxyphene ; pharmacokinetics ; half-life ; 3-compartment model ; steady state prediction ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Data from a previously published single dose study of d-propoxyphene 65 mg given i.v. to 8 healthy subjects have been subjected to non linear regression analysis by a curve-fitting program to test the applicability of a 2- and a 3-compartment open model. Analysis of residuals (difference between observed and computed concentrations) revealed similar systematic deviations in all 8 subjects when the 2-compartment model was used (5–10 h negative residuals, after 13 h positive residuals). In contrast, curve-fit by a 3-compartment model (with two parallel peripheral compartments) was good with no systematic deviations. The data show that a terminal monoexponential decline in d-propoxyphene concentrations cannot be expected until 15–30 h after single dose administration, and that the determination of the corresponding half-life is rather inaccurate. Accordingly, precise steady state level predictions may be difficult to obtain from conventional single dose studies with d-propoxyphene.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00541937
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  • 100
    Electronic Resource
    Electronic Resource
    Acetaminophen accumulation in pediatric patients after repeated therapeutic doses (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 57-59 
    Details
    ISSN: 1432-1041
    Keywords: acetaminophen ; pediatric patients ; fever therapy ; accumulation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acetaminophen serum concentrations were studied in 21 infants and children with fever. The maximum serum concentrations ranged from 9.96 to 19.6 µg/ml after a single dose of 12–14 mg/kg and 13.9 to 40.1 µg/ml after a single dose of 22–27 mg/kg. Ten patients were restudied at steadystate after repeat doses had been given every 4 or 8 h for 1 to 3 days. Total area under the acetaminophen serum concentration-time curve normalized for dose averaged 0.181 (ml/min/kg)−1 after the first dose and 0.202 (ml/min/kg)−1 at steady-state (p〈0.05). Five patients showed a 13 to 44% increase in the AUC; one had a 10% decrease in the AUC; and four had less than 6% change in the AUC. There was no evidence of hepatotoxicity. These data suggest that acetaminophen may accumulate after repeated therapeutic doses in children with fever.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02395207
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