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-QNB; K1 values were 7 x 10(-6) M for the taenia and 2 x 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.
Ishida
Y
Y
Department of Pharmacology, School of Medicine, University of Hawaii, Honolulu 96822.
Mizukami
M
M
Taniguchi
T
T
Satake
N
N
Fujiwara
M
M
Shibata
S
S
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001667:Binding, Competitive; D002217:Carbachol / Q000494:pharmacology; D002432:Cecum / Q000187:drug effects; D004206:Disopyramide / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007422:Intestines / Q000187:drug effects; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D010276:Parasympatholytics; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects*
D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D011813:Quinuclidinyl Benzilate; D001285:Atropine; D006632:Histamine; D002217:Carbachol; D004206:Disopyramide; D000109:Acetylcholine