Selective antagonists provide evidence that M1 muscarinic receptors may mediate carbachol-induced drinking in the rat

Eur J Pharmacol. 1990 Apr 10;179(1-2):159-65. doi: 10.1016/0014-2999(90)90413-z.

Abstract

The present study served to investigate the ability of seven selective muscarinic antagonists to inhibit carbachol-induced drinking in the rat. The muscarinic antagonists were given by intracerebroventricular (i.c.v.) injection 1 min before the i.c.v. injection of carbachol (1 microgram/rat). The M2 antagonist, methoctramine, was inactive up to 80.3 nmol/rat. The M3 antagonist, p-fluoro-hexahydro-sila-difenidol, elicited a modest (42%) but statistically significant inhibition of drinking only at 80 nmol/rat. On the other hand, the selective M1 antagonists, (R)-trihexphenidyl, o-methoxy-sila-hexocyclium and pirenzepine, produced a marked and dose-dependent inhibition of carbachol-induced drinking, their ID50 values being 0.51, 7.36 and 9.31 nmol/rat. Also the M1/M3 antagonists, 4-diphenylacetoxy-N-methylpiperidine methiodide and hexahydro-sila-difenidol, were potent inhibitors of carbachol-induced drinking, their ID50 values (0.28 and 11.09 nmol/rat) being related to their pA2 values for M1 receptors in rabbit vas deferens. These data suggest that carbachol-induced drinking may be mediated by activation of muscarinic M1 receptors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / administration & dosage
  • Angiotensin II / pharmacology*
  • Animals
  • Carbachol / administration & dosage
  • Carbachol / antagonists & inhibitors
  • Carbachol / pharmacology*
  • Dose-Response Relationship, Drug
  • Drinking / drug effects*
  • Injections, Intraventricular
  • Male
  • Muscarinic Antagonists
  • Pirenzepine / administration & dosage
  • Pirenzepine / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Muscarinic / drug effects*

Substances

  • Muscarinic Antagonists
  • Receptors, Muscarinic
  • Angiotensin II
  • Pirenzepine
  • Carbachol