ANTICHOLINERGIC ACTION OF DISOPYRAMIDE IN INTESTINAL SMOOTH-MUSCLE OF THE GUINEA-PIG - INHIBITION OF MUSCARINIC RECEPTORS (M1 AND M2)

Antimuscarinic actions of disopyramide were investigated by measuring the contractile responses of intestinal smooth muscles and ligand binding in cardiac and intestinal membrane preparations. Disopyramide caused a parallel shift of the dose-response curves for acetylcholine, McN-A-343, and carbachol to the right in the guinea pig taenia caeci; pA2 values were 5.4 for acetylcholine, 5.5 for McN-A-343 and 5.9 for carbachol. In the guinea pig ileum, disopyramide competitively antagonized acetylcholine in the contractile responses, having the pA2 value of 6.1. In microsomal fractions of the guinea pig taenia caecum and heart, disopyramide was capable of replacing 3H-ONB; Ki values were 7×10-6 M for the taenia and 2×10-6 M for the heart. These results suggest that disopyramide exerts antimuscarinic action through M1 and M2 receptors with a potency approximately 3 times greater for M2 than M1. © 1990, The Japanese Pharmacological Society. All rights reserved.