Christopoulos_1997_Eur.J.Pharmacol_339_153

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.