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  • 1
    Digitale Medien
    Digitale Medien
    Reduction in phenytoin clearance caused by cimetidine (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 135-137 
    Details
    ISSN: 1432-1041
    Schlagwort(e): phenytoin ; drug interactions ; cimetidine ; inhibition of metabolism ; disposition kinetics ; mixed function oxidases
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00544030
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  • 2
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Peristaltic reflex ; Intestinal motility ; Sympathetic denervation ; Supersensitivity ; Adrenoceptors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00506194
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  • 3
    Digitale Medien
    Digitale Medien
    5-HT mediated GABA excitatory responses in the guinea-pig proximal ileum (1983)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 324 (1983), S. 180-184 
    Details
    ISSN: 1432-1912
    Schlagwort(e): GABA ; 5-Hydroxytryptamine ; Guinea-pig ileum ; Desensitization
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 1. GABA (3–100 μM) and 5-HT (0.03–30 μM) caused concentration-dependent transient contractions of the longitudinal muscle of the guinea-pig ileum. 2. The contractile response to GABA was antagonized by hyoscine (2.2 μM), TTX (0.7 μM), bicuculline (3 μM), furosemide (25 μM) and desensitization to GABA itself, while hexamethonium (20 μM) and methysergide (20 μM) were without effect. 3. The contractile response to 5-HT was antagonized by hyoscine (2.2 μM), TTX (0.7 μM) and desensitization to 5-HT itself and was unaffected by bicuculline (10 μM), hexamethonium (20 μM), furosemide (25 μM) and methysergide (20 μM). 4. A desensitization procedure that caused a 84.7-fold increase in the 5-HT EC50 also resulted in a 74.1-fold increase of the GABA EC50. Desensitization to GABA caused a reduction of 5-HT induced response but only in preparations desensitized by high (50 μM) concentrations of GABA. 5. The results indicate that GABA-induced contractions in the guinea-pig ileum are mediated by activation of cholinergic motor neurones. This effect appears to be mediated by interneuronal release of 5-HT rather than by a direct stimulatory action of GABA on the effector neurones.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00503891
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