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  • 1
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This work reports a study of the effects of elliptinium on heart rate, arterial blood pressure and capillary permeability in guinea-pigs. The variations in capillary permeability are determined by spectrophotometric assay of skin Evans blue. Elliptinium induces dose-independent tachycardia and dose-related hypotension. For the highest dose (6 mg/kg), elliptinium induces lethal collapsus. Elliptinium increases capillary permeability and this effect, particularly marked at 1 mg, i.d., is partially antagonized by mepyramine-cimetidine association. These results are discussed in comparison with those obtained with elliptinium on other parameters, with histamine and with different antitumoral agents. The increase in capillary permeability raises the question of its relevance to the anticancer activity of elliptinium.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 113 (1997), S. 81-87 
    ISSN: 1432-1106
    Keywords: Serotonin ; Nociception ; Spinal cord ; Pain tests ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The involvement of serotonin (5-HT) in the modulation of nociceptive impulse in the spinal cord has been widely studied. However, its activity, considering the nature of noxious stimuli and the type of 5-HT receptors involved, merits to be further elucidated. The present behavioural study was performed to compare the doseantinociceptive effect relationship of 5-HT in rats, after intrathecal, (i.t.) injection (10 μl/rat), using mechanical (paw pressure), thermal (tail immersion and tail-flick) and chemical (formalin) pain tests. In rats submitted to the paw pressure test, 5-HT was found to possess a dose-dependent antinociceptive activity (0.01, 0.1, 1, 10 and 20 μg/rat) when vocalization threshold was assessed as a pain parameter. A peak effect occurred 5 min after the injection and the effect was maintained for 45 min. The lowest active dose was 0.1 μg (maximum increase in vocalization thresholds, 23±3%) and a plateau was observed for 10 μg and 20 μg (maximum increase in vocalization thresholds, 72±7% and 71±6%, respectively). When paw withdrawal was assessed, 5-HT induced a weak hyperalgesic effect for the highest dose (60μg), while other doses were ineffective. In the tail-immersion (warmth and cold) and tail-flick tests, different doses (0.01, 0.1, 1, 10, 30, 60 and 100 μg/rat), were studied. In the two immersion tests, only the highest doses (60 μg and 100 μg) significantly increased the withdrawal thresholds from 5 to 45 min after the injection. The maximum effect was observed at 5 min (23±4% and 21±6% for 60 μg; 27±3%, and 30±6% for 100 μg in the warmth and cold immersion test, respectively). In the tail-flick test, the doses of 30, 60 and 100 μg/rat dose-dependently and significantly increased the withdrawal thresholds from 5 to 45 min after the injection, with a maximum effect at 5 min (30±5% for 30 μg; 37±6% for 60 μg; and 45±4% for 100 μg). In the formalin test, 5-HT (10, 25, 50, 75 and 100 μg/rat) produced dose-related antinociception. The nociceptive response (licking of the injected paw) was significantly reduced from 25 μg (−59±11%) in the early phase, whereas the lowest active dose in the late phase was 50 μg (−46±17%). For both phases, a total inhibition was obtained with 100 μg. It is concluded that the effect of 5-HT on pain tests may differ according to the applied stimulus and the parameter assessed; unspecific effects of 5-HT may modify motor reactions to noxious stimuli. Mechanical test (assessment of vocalization) was the most sensitive to 5-HT. These observations are of importance in order to further study the pharmacological mechanisms involved in 5-HT spinally induced antinociception.
    Type of Medium: Electronic Resource
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  • 3
    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
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  • 4
    ISSN: 1432-1041
    Keywords: Parkinson's disease ; Apomorphine ; pharmacokinetics ; adverse effect ; on-off effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five patients with Parkinson's disease were given a single sublingual dose of apomorphine in 3 mg tablets (2 patients received 18 mg and 3 patients took 39 mg). The therapeutic effect appeared within 33.0 min and lasted 137 min. There was a significant correlation between peak concentration, area under the curve, dose (mg/kg) and the duration of the therapeutic effect.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Chromatography B: Biomedical Sciences and Applications 584 (1992), S. 249-255 
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 5 (1981), S. 233-236 
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous work on Hydroxy-9-methyl-2-ellipticinium acetate indicated a bronchoconstrictor activity which could be partially offset by antagonists of the H1 histamine receptors, and the absence of any direct effect on smooth muscle. OH-9-CH3-2-E at concentrations of 10 μg/ml and 500 μg/ml produced a moderate and a variable release of histamine when placed in contact with whole human blood and lung fragments, respectively. In addition, at a dose of 3 mg/kg in the guinea pig, pulmonary airway resistance was raised and the blood histamine level lowered. A significant correlation was found between these two effects. These results demonstrate that OH-9-CH3-2-E possesses a histamine-releasing potency which is partly responsible for its bronchial effects, implying that precautions may have to be taken when it is used as a therapeutic agent in sensitive subjects. However, the moderate intensity of this potency has not so far precluded therapeutic use of the preparation.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2072
    Keywords: Learned-helplessness ; Depression ; Morphine ; Naloxone ; Mu-opioid receptors ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to investigate the possible involvement of the mu-opioid system on the learned-helplessness paradigm, an experimental model of depression, in rats. In this test, rats were first exposed to inescapable foot-shocks (IS); 48 h later, they were submitted to a daily shuttle-box session (30 trials) for 3 consecutive days. Avoidance responses, escape failures and animal activity during each intertrial interval were recorded. Twice daily injections of morphine (0.25–8 mg/kg per day, SC), a mu-opioid agonist, reduced the increased escape failures induced by IS, as did tricyclic antidepressants. Significantly higher intertrial activity was observed in rats treated with morphine (2–8 mg/kg per day) compared with their associated control groups. Naloxone (1 and 2 mg/kg, IP), a mu-opioid antagonist, injected 10 min before each shuttle-box session impaired escape behavior in non-stressed rats and worsened the escape deficit induced by IS. Morphine-induced improvement of escape behavior and increase in intertrial activity were clearly reversed by a low inactive dose of naloxone (0.5 mg/kg). These results suggest that mu-opioid receptor mediation is involved in the deleterious effects of uncontrollable stress.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 93 (1987), S. 515-519 
    ISSN: 1432-2072
    Keywords: Clomipramine ; Morphine ; Tricyclic antidepressants ; Forced swimming test ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tricyclic antidepressant-morphine interactions have been extensively studied on pain tests but less often on tests predictive of antidepressant activity. The effects of clomipramine (CMI) and morphine were tested on the forced swimming test in mice after pretreatment with CMI, morphine or saline. Like CMI, though less so, morphine was significantly active. Morphine pretreatment partially inhibited the effect of CMI irrespective of the morphine pretreatment dose, but reduction of morphine activity by CMI was non-significant. Acquired tolerance to morphine occurred, but not to CMI. The mechanisms at work were discussed. CMI and desmethylclomipramine (DCMI) plasma levels remained the same after morphine pretreatment, ruling out a pharmacokinetic mechanism. The interaction implied involvement of opiate systems. CMI might have been acting on two different opiate receptor populations, one sensitive to morphine pretreatment, the other not. The mechanism of this action seems to be different from that of morphine.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This work reports a study of cardiovascular effects of elliptinium, a recently-acquired antitumoral agent, acutely administered i.v. in the dog. Its hemodynamic effects (10 parameters) are detailed, and their mechanism of action is investigated by antagonist administration and determination of blood and plasma histamine levels. Elliptinium induces vasodilation and tachycardia. The former is mainly due to histamine release, and a brief and slight release of prostaglandins; the latter is due to a reflex to hypotension and release of catecholamines. These results agree with others using various compounds of the ellipticine family and anthracycline antitumoral agents. They suggest treatment to prevent anaphylactoid side effects observed with this drug in man and they raise the question of the usefulness, in an anti-tumoral agent, of histamine releasing properties.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1573-6822
    Keywords: diabetes ; rat ; cell culture ; antidepressant ; kinetics ; biotransformation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Biotransformation of amitriptyline (AMI) was studied at different intervals in freshly isolated hepatocytes from healthy or streptozocin-induced diabetic rats in order to investigate the influence of the diabetic state. Levels of free and conjugated AMI, demethylated and hydroxylated metabolites, were assessed by HPLC analysis. In hepatocytes isolated from diabetic rats, AMI was less completely metabolized and the demethylation reaction became more important than in non-diabetic rat hepatocytes. Although the proportions of hydroxylated metabolites decreased in diabetic rats, it always remained predominant. Furthermore, glucuronidation of metabolites was greater, especially for (Z)-10-hydroxynortriptyline in diabetic animals.
    Type of Medium: Electronic Resource
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