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  • 1
    Electronic Resource
    Electronic Resource
    The time course of functional and morphological changes of the guinea-pig colon after “a frigore” denervation of the periarterial sympathetic nerves (1972)
    Springer
    Acta neuropathologica 22 (1972), S. 190-199 
    Details
    ISSN: 1432-0533
    Keywords: Fluorescence Histochemistry ; Sympathetic Denervation ; Periarterial Nerve Stimulation ; Regenerating Adrenergic Nerves
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary After sympathetic denervation of the guinea-pig distal colon the time course and the relationship between morphological and functional changes were studied, by using the fluorescence method and by evaluating the response of longitudinal muscle to periarterial nerve stimulation. The inhibitory response to sympathetic nerve stimulation was completely abolished 48 h after denervation. Tissue catecholamines can no longer be detected in either the intramural vessels or in the intramural plexuses 96 h after denervation, and in no preparation could they be observed again until 24 days after denervation. After 30 days catecholamines stores slowly began to reappear and were completely restored only 100–120 days after denervation. During the whole period of reinnervation the response to periarterial nerve stimulation was lacking. The inhibitory effect could be elicited only 130 days after denervation and before the morphological pattern had been completely restored.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00684522
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacological activity and safety of trandolapril (RU 44570) in healthy volunteers (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 149-153 
    Details
    ISSN: 1432-1041
    Keywords: Trandolapril ; ACE inhibition ; pharmacodynamics ; duration ; healthy volunteers ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacological activity and safety of the new angiotensin converting enzyme (ACE) inhibitor trandolapril (RU 44570) has been evaluated in ten healthy male volunteers given 2 mg once daily for seven days. Assessment criteria included evaluation of plasma ACE and renin activity and aldosterone levels in the supine and standing positions, monitoring of blood pressure, heart rate and electrocardiogram, routine blood and urine laboratory tests, and evaluation of adverse effects. Plasma ACE activity (both in the supine and standing positions) was significantly lower after the first dose and was almost completely suppressed after 7 days of treatment. Plasma renin activity with the subjects in both positions was significantly increased at the end of treatment. Plasma aldosterone did not vary significantly, except for an increase in the standing position after 7 days of washout. No significant changes occurred in blood pressure, heart rate, electrocardiogram, blood or urine laboratory tests. No adverse effects were reported, in particular, no orthostatic hypotension, cough or episodes of bronchospasm occurred. It is concluded that oral trandolapril 2 mg o.d. is an effective and long-lasting ACE inhibitor with a good safety profile on repeated dosing. Further studies are warranted to investigate its therapeutic application as well as its safety profile after long-term administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280069
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  • 3
    Electronic Resource
    Electronic Resource
    Comparative effects of rifabutin and rifampicin on hepatic microsomal enzyme activity in normal subjects (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 595-599 
    Details
    ISSN: 1432-1041
    Keywords: rifampicin ; rifabutin ; microsomal enzyme induction ; healthy volunteers ; antimicrobial agent
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The comparative enzyme inducing effects of rifabutin and the chemically related drug rifampicin have been investigated in 8 normal subjects. Rifampicin 600 mg daily for 7 days caused considerable shortening of the antipyrine half-life and a marked increase in antipyrine clearance, associated with an increased rate of conversion to norantipyrine and, to a lesser extent, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine. The urinary excretion of 6-β-hydroxycortisol was also markedly increased, while plasma GGT activity showed only a slight albeit statistically significant elevation. In the same subjects, rifabutin in the proposed therapeutic dosage (300 mg daily) for 7 days also enhanced the metabolic elimination of antipyrine, with preferential stimulation of the demethylation pathway, and increased the excretion of 6-β-hydroxycortisol, but the magnitude of the effects was signifiantly less than after rifampicin. No significant change in plasma GGT was seen. The results indicate that, contrary to the findings in animals, rifabutin does have enzyme inducing properties in man, although at the dosages assessed they were considerably less than those of rifampicin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00615223
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  • 4
    Electronic Resource
    Electronic Resource
    Reduction in phenytoin clearance caused by cimetidine (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 135-137 
    Details
    ISSN: 1432-1041
    Keywords: phenytoin ; drug interactions ; cimetidine ; inhibition of metabolism ; disposition kinetics ; mixed function oxidases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of cimetidine on the disposition kinetics of phenytoin was investigated in 7 healthy volunteers. Each subject received a single intravenous dose of phenytoin on two occasions, in the control state, and during concurrent treatment with cimetidine 1200 mg/day for 6 days. A slight but statistically significant decrease both in the rate of elimination and total body clearance of phenytoin was observed during the administration of cimetidine. The effect is probably due to inhibition of metabolism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544030
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  • 5
    Electronic Resource
    Electronic Resource
    Subsensitivity of enteric cholinergic neurones to α2-adrenoceptors agonists after chronic sympathetic denervation (1985)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 329 (1985), S. 271-277 
    Details
    ISSN: 1432-1912
    Keywords: Enteric neurones ; Acetylcholine release ; Sympathetic denervation ; α2-Adrenoceptors ; Yohimbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The concentration-effect relationships of noradrenaline, dopamine and clonidine in inhibiting resting and stimulated acetylcholine output have been studied in intact and in sympathetically denervated preparations of guineapig isolated distal colon. 2. The order of potencies for the inhibition of resting acetylcholine release in intact preparations was clonidine 〉 dopamine 〉 noradrenaline while the order of intrinsic activities was noradrenaline 〉 dopamine 〉 clonidine. 3. Sympathetic denervation was able to modify the potency of either clonidine, dopamine and noradrenaline. Noradrenaline was 6 times more potent in inhibiting resting acetylcholine release in denervated than in intact preparations, while clonidine and dopamine underwent a 18-fold and a 11-fold decrease in potency after denervation. The potency of clonidine relative to noradrenaline was 110 in intact preparations and only 1.2 in denervated organs. The intrinsic activities of noradrenaline, dopamine and clonidine were almost unchanged in denervated organs. 4. A dose-dependent facilitatory effect of yohimbine on both the resting acetylcholine output and the peristaltic reflex could be observed in intact but not in sympathetically denervated preparations at concentrations ranging from 2.5×10−8 M to 2.5×10−7 M. 5. Yohimbine was able to counteract the inhibitory effect of dopamine and to remove the inhibitory effect of periarterial nerve stimulation on both acetylcholine release and the peristaltic reflex. 6. Our results are consistent with the existence of a tonic physiological modulation of enteric cholinergic neurones by postganglionic sympathetic fibres. The order of potencies of adrenoceptor agonists and the antagonism by yohimbine is consistent with such a modulation being entirely carried out through α2-heteroceptors. To what extent pre- or post-junctional factors are involved in the denervation-induced effect cannot be established with certainty from our results. However the pattern of denervation-induced potency changes for noradrenaline, clonidine and dopamine and the difference in their intrinsic activities on α2-adrenoceptors strongly suggest the prevalence of prejunctional factors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00501879
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  • 6
    Electronic Resource
    Electronic Resource
    On the ability of caerulein to increase propulsive activity in the isolated small and large intestine (1971)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 268 (1971), S. 44-58 
    Details
    ISSN: 1432-1912
    Keywords: Caerulein ; Cholecystokinin Pancreozymin ; Peristaltic Reflex ; Intestinal Propulsion ; Myenteric Plexus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Caerulein increased the efficiency of the peristaltic reflex both in the large and small intestine. Such an effect could be evidenced by measuring the velocity of propulsion of a solid bolus in the colon and the amount of ejected fluid in the fatigued ileum. The effect on propulsion was related to the concentrations employed and log dose-response curves could be constructed. 2. Caerulein was able to counteract the inhibitory effect of mild cooling (25 to 28
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00997172
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  • 7
    Electronic Resource
    Electronic Resource
    Abstracts (1971)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 269 (1971), S. 385-494 
    Details
    ISSN: 1432-1912
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01003053
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  • 8
    Electronic Resource
    Electronic Resource
    Changes in sensitivity to the inhibitory effects of adrenergic agonists on intestinal motor activity after chronic sympathetic denervation (1984)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 325 (1984), S. 145-152 
    Details
    ISSN: 1432-1912
    Keywords: Peristaltic reflex ; Intestinal motility ; Sympathetic denervation ; Supersensitivity ; Adrenoceptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The concentration-effect relationships of adrenergic agonists in inhibiting muscular tone, carbachol-induced contraction of circular muscle strips and nerve-mediated motor activity during the peristaltic reflex have been studied in intact and sympathetically denervated preparations of isolated guinea-pig colon. 2. The order of potencies of adrenergic agonists was different for muscular and nerve-mediated effects, being clonidine 〉 noradrenaline 〉 methoxamine 〉 isoprenaline for the inhibition of peristalsis and isoprenaline 〉 noradrenaline 〉 methoxamine 〉 clonidine for the relaxation of circular muscle. 3. Denervation supersensitivity was specific for the adrenergic agonists and developed both to the muscular and nerve-mediated effects, involving both α and β receptors. The degree of potentiation was similar for noradrenaline and isoprenaline when measured for the muscular effects but was significantly higher for noradrenaline than for isoprenaline or methoxamine when measured for peristalsis inhibition. No potentiation could be observed for papaverine and for the muscular effects of methoxamine and phenylephrine. The increase in potency of noradrenaline ranged from a 26-fold increase for the inhibition of propulsion velocity to a 2.5-fold increase for the inhibition of carbachol-induced contraction. A much narrower range was observed for isoprenaline. Potentiation could also be observed for the inhibitory effect of noradrenaline on acetylcholine release. 4. Clonidine was the most potent agonist against peristaltic reflex and the weakest agonist in relaxing circular muscle. Denervated preparations became subsensitive to the inhibitory effect of clonidine on peristaltic reflex. The potency of clonidine relative to noradrenaline was 488 in intact preparations and only 3.1 in denervated organs. 5. Our results are consistent with a main role played by β receptors in the relaxation of circular smooth muscle and with a selective involvement of α2 receptors in peristalsis inhibition. The pattern of sensitivity changes is consistent with a high degree of physiological modulation by sympathetic supply both on the smooth muscle and on the intramural nervous structures. Both pre- and postjunctional mechanisms could be responsible for the development of supersensitivity, but the former seem to operate only at interneuronal synapses. The opposite sensitivity changes observed for noradrenaline and clonidine suggest a different effect of two agonists at the presynaptic level.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00506194
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  • 9
    Electronic Resource
    Electronic Resource
    Pharmacological studies of the rabbit and human renal pelvis (1974)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 285 (1974), S. 209-222 
    Details
    ISSN: 1432-1912
    Keywords: Renal Pelvis Smooth Muscle ; Sympathomimetic Amines ; Transmural and Periarterial Stimulation ; α-adrenoceptors ; Adrenergic Blocking Agents ; Fluorescence Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The responses of the isolated rabbit and human renal pelvis to drugs and to electrical stimulation have been investigated. Regular spontaneous changes in tension occur in the circular smooth muscle, which in the rabbit are synchronous with electrical waves. The responses to electrical stimulation seem to be due to the release of catecholamines from adrenergic nerves. Such nerves have been observed by means of a fluorescence technique. The cholinergic system appears functionally unimportant. The adrenergic responses in human and rabbit seem to be mediated exclusively by α-adrenoceptors. The denervated rabbit organ shows hypersensitivity, mainly to low concentrations of adrenaline. The failure of uptake inhibitors to potentiate the responses to noradrenaline seems in favour of postsynaptic hypersensitivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00498991
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  • 10
    Electronic Resource
    Electronic Resource
    Effects of pentazocine on the intestine and biliary tract of the rabbit in vitro (1977)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 299 (1977), S. 207-210 
    Details
    ISSN: 1432-1912
    Keywords: Pentazocine ; Ileum ; Colon ; Bile duct ; Extracellular electrical activity ; Acetylcholine release
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pentazocine impairs peristaltic activity and relaxes longitudinal muscle in the colon and in the ileum. The circular coat is excited in the colon, while in the ileum pentazocine exhibits both excitatory and inhibitory effects depending on the concentration employed. Pentazocine does not exert a spasmogenic effect in the smooth muscle of terminal bile duct but instead reduces the electrically-induced contraction. The effect of pentazocine does not seem to involve endogenous acetylcholine or catecholamine release.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00500312
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