Mechanism of catecholamine antagonism in rat heart produced by pilocarpine and related drugs.

1 High concentrations of pilocarpine and methacholine consistently lowered the potencies of a series of adrenoceptor agonists as shown by displacement of complete cumulative dose-effect curves for their positive chronotropic action on rat isolated atria. The order of potency of the agonists was characteristic of beta-adrenoceptor activation and this was converted to the type which characterizes alpha-adrenoceptor activation when pilocarpine was present.2 Propranolol effectively blocked the adrenoceptor agonists in the presence of pilocarpine and phentolamine abolished the antagonistic actions of pilocarpine. Atropine, which by itself did not affect the action of the adrenoceptor agonists, abolished both the bradycardia and antagonism produced by pilocarpine.3 It is concluded that pilocarpine antagonizes adrenoceptor agonists by muscarinic cholinoceptor activation without involving classical adrenoceptors.