The relative potencies of some agonists at M2 muscarinic receptors in guinea-pig ileum, atria and bronchi

Abstract

The effects of some agonists on isolated preparations of guinea-pig ileum, atria and bronchial muscle have been compared with those of carbachol. The concentrations producing comparable responses were used to estimate the equipotent molar ratio relative to carbachol. Arecaidine propargyl ester was 4 to 5 times as active as carbachol on the ileum but more than 10 times as active as carbachol on atrial rate or atrial force, so the results confirm that this compound has a 2 to 3 fold selectivity for receptors in atria. Ethoxyethyltrimethylammonium iodide was one-quarter to one-third as active as carbachol on ileum but only one-tenth as active as carbachol on atrial rate or atrial force and so shows a 3 to 4 fold selectivity for receptors in ileum. The other compounds tested, which included acetylcholine, methacholine, n-pentyltrimethyl-ammonium iodide and bethanechol showed less selectivity. There were no obvious differences between effects on atrial rate and effects on atrial force, though with esters it was often difficult to obtain effects on atrial rate in the absence of an inhibitor of cholinesterase. Activity on bronchial muscle was generally similar to activity on ileum.