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

• Published in: European journal of pharmacology Vol. 364; no. 1; pp. 7 - 11
• Main Authors: Mayorga, Arthur J, Cousins, Michael S, Trevitt, Jennifer T, Conlan, Aimee, Gianutsos, Gerald, Salamone, John D
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 1999; Elsevier
• Subjects: Acetylcholine; Animals; Biological and medical sciences; Corpus Striatum - drug effects; Corpus Striatum - physiopathology; Diamines - pharmacology; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Jaw - drug effects; Jaw - physiopathology; Male; Medical sciences; Motor; Muscarinic Agonists - toxicity; Muscarinic Antagonists - pharmacology; Parkinson's disease; Pharmacology. Drug treatments; Pilocarpine - toxicity; Pirenzepine - analogs & derivatives; Pirenzepine - pharmacology; Rats; Rats, Sprague-Dawley; Receptor, Muscarinic M1; Receptor, Muscarinic M2; Receptor, Muscarinic M3; Receptor, Muscarinic M4; Receptors, Muscarinic - drug effects; Receptors, Muscarinic - physiology; Scopolamine - pharmacology; Toxicity: nervous system and muscle; Tremor; Tremor - chemically induced; Tremor - physiopathology; Vacuous chewing; Acetylcholine; Parkinson's disease; Vacuous chewing; Tremor; Motor; Jaw; Intraperitoneal administration; Rat; Toxicity; Parkinson disease; Pilocarpine; Involuntary movement; Cholinergic receptor; Degenerative disease; Antagonist; Neurological disorder; Mechanism of action; Nervous system diseases; M4 receptor; Rodentia; Antiparkinson agent; Biological activity; Cerebral disorder; Parasympathomimetic; Vertebrata; Mammalia; Animal; Central nervous system disease; Body movement; Muscarinic receptor; Parasympatholytic; Extrapyramidal syndrome
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(98)00811-5

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.