The effects of drugs inhibiting catecholamine uptake on tyramine and noradrenaline-induced contractions of the isolated rat vas deferens.
1. Cocaine did not antagonize the tyramine-induced contractile response of the isolated rat vas deferens at the same concentrations which markedly potentiated the contractile response to noradrenaline.2. Imipramine and amitriptyline non-competitively antagonized the contractile response to tyramine but did not potentiate noradrenaline. Desmethylimipramine produced both potentiation of noradrenaline and antagonism of tyramine.3. Dexchlorpheniramine non-competitively antagonized the contractile response to tyramine. It also produced an atypical potentiation of noradrenaline in which lower concentrations of noradrenaline were potentiated to a greater extent than higher ones.4. Imipramine inhibited the in vitro uptake of noradrenaline-(3)H in rat vas deferens as did cocaine, desmethylimipramine and dexchlorpheniramine. These results suggest that the alpha-adrenergic blocking property of imipramine masks the potentiation of noradrenaline by uptake inhibition.5. Evidence is also presented which suggests that alpha-adrenergic blockade of released noradrenaline may be the major mechanism for tyramine inhibition by imipramine-like drugs. This may explain why cocaine, which has no real alpha blocking action, is ineffective against tyramine.
D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology; D004336:Drug Antagonism; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D014316:Tritium; D014439:Tyramine / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects*
D002395:Catecholamines; D014316:Tritium; D003042:Cocaine; D007099:Imipramine; D009638:Norepinephrine; D014439:Tyramine