Characterization of the muscarinic receptor subtype mediating pilocarpine-induced tremulous jaw movements in rats

Abstract

Four muscarinic receptor antagonists with varying selectivities for the four pharmacologically-defined muscarinic receptor subtypes (M 1–M 4) were administered into the lateral ventricle to determine their relative potency in reducing tremulous jaw movements induced by i.p. injection of the muscarinic receptor agonist pilocarpine (4.0 mg/kg). All four muscarinic receptor antagonists reduced tremulous jaw movements in a dose-dependent manner, with the following rank order of potency: scopolamine>methoctramine≥telenzepine>pirenzepine. This pattern is inconsistent with the rank order of affinity of these agents at the muscarinic M 1 receptor, and is consistent with their rank order of affinity at muscarinic M 2 or M 4 receptors. Because tremulous jaw movements are related to striatal function, and the muscarinic M 4 receptor is more predominant than the muscarinic M 2 receptor as a post-synaptic receptor in striatum, the present results suggest that pilocarpine induces jaw movements due to muscarinic M 4 receptor stimulation. In view of the hypothesized relation between parkinsonism and cholinomimetic-induced jaw movements, these data suggest that a centrally-acting muscarinic M 4 receptor antagonist could be useful as an antiparkinsonian agent.