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Journal of Pharmacology And Experimental Therapeutics, Vol. 99, Issue 3, 343-349, 1950
Copyright © 1950 by American Society for Pharmacology and Experimental Therapeutics

CORONARY DILATOR ACTION

I. Quantitative Assay in the Intact Dog

Martin M. Winbury 1, Patricia M. Michiels 1, W. E. Hambourger 1, Willard J. Stockfisch 1, and Donald L. Cook 1

1 Pharmacology Department, Division of Biological Research, G. D. Searle & Co., Chicago, Illinois

A method is presented for the quantitative assay of coronary dilator compounds in the intact dog. Coronary inflow to the anterior descending branch of the coronary artery is recorded with a rotameter. Cardiac output, mean blood pressure, peripheral resistance and cardiac work are determined simultaneously with coronary flow changes.

All compounds are injected into the coronary circuit. The assay is carried out on a modified factorial design in which two or three logarithmically graded doses of a test compound are alternated with the same number of doses of a standard, dicyclohexylamine-beta-diethylaminoethylcarbamate hydrochloride. This compound appears to be a coronary dilator which has no cardiovascular side actions in the experiments described. A single assay in each of three animals usually suffices for a potency estimate with a standard error of 25 per cent or less of the mean value. Aminophylline assayed by this method was found to average 15.3 per cent of the activity of the standard.

Submitted on March 21, 1950






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