PHARMACOLOGICAL ANALYSIS OF THE MODE OF INTERACTION OF MCN-A-343 AT ATRIAL MUSCARINIC M-2 RECEPTORS

The mode of interaction of the muscarinic M-2 receptor partial agonist , McN-A-343 (4-(m-chlorophenylcarbamoyloxy)-2-butynyltri methylammoniu m), was investigated in the electrically-driven guinea-pig left atrium . Comparison of the negative inotropic responses to this agent with th ose of the full agonist, carbachol, followed by operational model-fitt ing, yielded estimates of the dissociation constant (K-A) and efficacy (tau) of McN-A-343. Following partial receptor inactivation with prop ylbenzylcholine mustard, the properties of McN-A-343 as an inhibitor o f 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 K-B of McN-A-343 as an antagonist wa s -4.65 +/- 0.06, and was not significantly different from the log K-A of this agent as an agonist. (C) 1997 Elsevier Science B.V.