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Journal of Pharmacology And Experimental Therapeutics, Vol. 146, Issue 3, 354-358, 1964
Copyright © 1964 by American Society for Pharmacology and Experimental Therapeutics

THE DUAL MODE OF THE ANTISPASMODIC EFFECT OF DICYCLOMINE HYDROCHLORIDE

W. R. McGrath 1, R. E. Lewis 1, and W. L. Kuhn 1

1 Department of Pharmacology, The Wm. S. Merrell Co., Division of Richardson-Merrell Inc., Cincinnati, Ohio

Dicyclomine was evaluated and compared with atropine for its effect on dose-response curves of ACh, bradykinin, and histamine which were obtained by the cumulative dose-response technique in the isolated guinea-pig ileum.

Dicyclomine antagonized ACh through a dual mode of action, having a noncompetitive as well as competitive effect. Atropine, at concentrations up to 1.7 x 10-7 molar exerted only a competitive antagonism of ACh. Dicyclomine antagonized bradykinin and histamine noncompetitively while atropine at the high concentration of 1.7 x 10-6 molar did not affect the responses to either bradykinin or histamine. A comparison of the affinity of dicyclomine for the noncompetitive receptor involved with the response to ACh, bradykinin, and histamine indicated that each of these agonists is antagonized by dicyclomine through a common mechanism.

Accepted on August 7, 1964






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Copyright © 1964 by the American Society for Pharmacology and Experimental Therapeutics.