Analysis of Miosis Produced by M c N-A-343 in Anesthetized Cats

ABSTRACT

M^cN-A-343 is a selective M₁ muscarinic agonist that stimulates muscarinic transmission in sympathetic ganglia. In preliminary experiments, we observed that i.v. M^cN-A-343 produced miosis in cats in the presence of nicotinic ganglionic blockade. This project was undertaken to ascertain the mechanism and site(s) by which M^cN-A-343 produces pupil constriction in the cat. Cats were anesthetized, the vago-sympathetic nerve trunks sectioned, and one superior cervical ganglion (SCG) was removed. Bilateral pupillary and nictitating membrane (NM) dose-response curves in response to i.v. M^cN-A-343 (6.25-1600 μg/kg) were generated during infusion of hexamethonium to block nicotinic ganglionic transmission. Experiments were repeated in animals pretreated with atropine or with the M₁ muscarinic receptor antagonist, pirenzepine. In one series of experiments, selective lesions of the ciliary ganglia were undertaken. M^cN-A-343 produced an atropine sensitive dose-related miosis that was potentiated by removal of the SCG but not antagonized by either pirenzepine or by removal of the ciliary ganglion. In contrast, contraction of the NM was blocked by both atropine and pirenzepine and was dependent on intact sympathetic ganglionic innervation. M^cN-A-343 induced pupillary constriction appears to be due to direct stimulation of the iris sphincter by stimulation of M₃ rather than M₁ muscarinic receptors. In contrast to sympathetic ganglia where muscarinic transmission (via M₁ muscarinic receptors) can readily be demonstrated, these results suggest a lack of muscarinic transmission in the parasympathetic ciliary ganglion.