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The affinity of pirenzepine and other antimuscarinic compounds for pre- and postsynaptic muscarine receptors of the isolated rabbit and rat heart.

To compare in one and the same organ the presynaptic muscarine receptors located at the postganglionic adrenergic nerves with postsynaptic receptors at the atrial myocardium, the affinities of pirenzepine were determined in the perfused rabbit heart and those of pirenzepine and N-methylatropine in the isolated rat heart. Methacholine was used as an agonist to decrease the stimulation-evoked overflow of either endogenous noradrenaline (rabbit heart) or previously incorporated 3H-noradrenaline (rat heart) by a presynaptic muscarine receptor mechanism, and to reduce the atrial tension development of either the spontaneously beating perfused rabbit heart or incubated rat left atria paced at 2 Hz (postsynaptic effect). The pA2 values of the antagonists calculated from the Schild plots were very similar and, thus, did not reveal differences in the receptor structure. It is concluded that pirenzepine does not differ from seven other antimuscarinic drugs which did not differentiate presynaptic receptors from postsynaptic ones in the rabbit or rat heart.