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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Functional determination of McN-A-343 affinity for M1 muscarinic receptors.

The affinity (KA) of 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium chloride (McN-A-343), acting as an agonist of M1 muscarinic receptors, has been estimated by means of fractional receptor inactivation, employing the irreversible muscarinic antagonist propylbenzylcholine mustard. Two M1-mediated responses elicited by McN-A-343 were studied: relaxation of the isolated rat duodenum and inhibition of twitch contractions in rabbit was deferens. A comparison was made with the affinity of McN-A-343 as an antagonist (KB) of acetylcholine-induced contraction in rat duodenum. Results showed that McN-A-343 displayed similar affinities as an agonist and as an antagonist: -log KA were 4.68 and 5.17 in duodenum and vas deferens, respectively, vs. -log KB of 4.96 in duodenum, indicating that the ability of McN-A-343 to selectively stimulate M1 receptors is not based on a greater affinity for this subtype. In both preparations examined, McN-A-343 reached maximum effect through occupation of a fraction of the total available receptors (approximately 30% in duodenum, approximately 80% in vas deferens), implying that occupation of M1 receptors is translated into effect in a highly efficient way.[1]


  1. Functional determination of McN-A-343 affinity for M1 muscarinic receptors. Micheletti, R., Schiavone, A. J. Pharmacol. Exp. Ther. (1990) [Pubmed]
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