Pharmacological analysis of the mode of interaction of McN-A-343 at atrial muscarinic M2 receptors

Eur J Pharmacol. 1997 Nov 27;339(2-3):153-6. doi: 10.1016/s0014-2999(97)01379-4.


The mode of interaction of the muscarinic M2 receptor partial agonist, McN-A-343 (4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium), was investigated in the electrically-driven guinea-pig left atrium. Comparison of the negative inotropic responses to this agent with those of the full agonist, carbachol, followed by operational model-fitting, yielded estimates of the dissociation constant (KA) and efficacy (tau) of McN-A-343. Following partial receptor inactivation with propylbenzylcholine mustard, the properties of McN-A-343 as an inhibitor of the carbachol-mediated responses were assessed. Analysis of the data, according to both competitive and allosteric models of interaction, favored the former model. The log KB of McN-A-343 as an antagonist was - 4.65+/-0.06, and was not significantly different from the log KA of this agent as an agonist.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / pharmacology*
  • Allosteric Regulation
  • Animals
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • Heart / drug effects*
  • Heart Atria / drug effects
  • Muscarinic Agonists / pharmacology*
  • Myocardial Contraction / drug effects
  • Receptor, Muscarinic M2
  • Receptors, Muscarinic / drug effects*
  • Receptors, Muscarinic / metabolism


  • Muscarinic Agonists
  • Receptor, Muscarinic M2
  • Receptors, Muscarinic
  • (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride