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

Four muscarinic receptor antagonists with varying selectivities for the fou r pharmacologically-defined muscarinic receptor subtypes (M-1-M-4) were adm inistered into the lateral ventricle to determine their relative potency in reducing tremulous jaw movements induced by i.p. injection of the muscarin ic receptor agonist pilocarpine (4.0 mg/kg). Ail four muscarinic receptor a ntagonists reduced tremulous jaw movements in a dose-dependent manner, with the following rank order of potency: scopolamine > methoctramine greater t han or equal to telenzepine > pirenzepine. This pattern is inconsistent wit h 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 func tion, and the muscarinic M-4 receptor is more predominant than the muscarin ic M-2 receptor as a post-synaptic receptor in striatum, the present result s suggest that pilocarpine induces jaw movements due to muscarinic M-4 rece ptor stimulation. In view of the hypothesized relation between parkinsonism and cholinomimetic-induced jaw movements, these data suggest that a centra lly-acting muscarinic M-4 receptor antagonist could be useful as an antipar kinsonian agent. (C) 1999 Elsevier Science B.V. All rights reserved.