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Published on: September 8, 2011
Methoctramine, a selective M2 alpha muscarinic receptor antagonist, does not inhibit carbachol-induced drinking in
M Massi1, C Polidori, C Melchiorre
1Institute of Pharmacology and Pharmacognosy, University of Camerino, Bologna, Italy.
Abstract:
Methoctramine, a selective M2 alpha muscarinic receptor antagonist, was examined for its ability to inhibit carbachol-induced drinking in the rat. Intracerebroventricularly (i.c.v.) administered methoctramine was devoid of activity up to a dose of 100 nmol/rat, whereas higher doses were toxic under our experimental conditions. 4-DAMP, pirenzepine and hexahydrosiladifenidol were also tested. The rank potency order for the compounds (4-DAMP greater than pirenzepine = hexahydrosiladifenidol) was similar to that for their affinity at M1 receptors, as found in experiments in vitro. The putative M1 agonist McN-A-343 was inactive up to doses of 13.9 micrograms/rat. Our data suggest that M2 alpha receptors do not mediate cholinergic drinking in the rat. The question whether M1 or M2 beta muscarinic receptors are involved in this response still awaits a firm answer.
Insights
Methoctramine, a selective M2 alpha muscarinic receptor antagonist, did not inhibit carbachol-induced drinking in rats. This suggests M2 alpha receptors are not involved in this drinking response.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Cholinergic pathways regulate drinking behavior in rats.
- Muscarinic receptors, specifically M1 and M2 subtypes, are implicated in various physiological processes.
Purpose of the Study:
- To investigate the role of M2 alpha muscarinic receptors in carbachol-induced drinking in rats.
- To determine if selective M2 alpha muscarinic receptor antagonism can inhibit this drinking behavior.
Main Methods:
- Intracerebroventricular administration of methoctramine, a selective M2 alpha muscarinic receptor antagonist, in rats.
- Testing other muscarinic receptor antagonists (4-DAMP, pirenzepine, hexahydrosiladifenidol) and an M1 agonist (McN-A-343).
- Observing the effects on carbachol-induced drinking behavior.
Main Results:
- Methoctramine did not inhibit carbachol-induced drinking at non-toxic doses.
- Higher doses of methoctramine exhibited toxicity.
- The potency order of other tested antagonists correlated with their M1 receptor affinity, suggesting M1 receptor involvement.
Conclusions:
- M2 alpha muscarinic receptors do not appear to mediate cholinergic drinking in the rat.
- The involvement of M1 or M2 beta muscarinic receptors in this response remains undetermined.
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