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Journal of Pharmacology And Experimental Therapeutics, Vol. 106, Issue 2, 166-179, 1952
Copyright © 1952 by American Society for Pharmacology and Experimental Therapeutics

THE PHYSIOLOGICAL DISPOSITION AND BIOTRANSFORMATION OF DIBENAMINE AND A METHOD FOR ITS ESTIMATION IN BIOLOGICAL TISSUES

Julius Axelrod 1, Lewis Aronow 1, and Bernard B. Brodie 1

1 Section on Chemical Pharmacology, National Heart Institute, National Institutes of Health, U. S. Public Health Service, Federal Security Agency, Bethesda, Maryland

Methods are described for the estimation of Dibenamine and one of its metabolites, dibenzylamine, in biological fluids and tissue.

Factors concerned with the physiological disposition and metabolic fate of Dibenamine in the dog after intravenous injection have been studied. Part of the drug is rapidly metabolized and part is localized in fat where it is stable and from which it slowly diffuses into the bloodstream. There is close correlation between the adrenergic blocking activity and the concentration of drug in fat.

No evidence that Dibenamine is hydrolyzed in the body to yield the corresponding alcohol was found. Most if not all the Dibenamine is dealkylated to form dibenzylamine. This compound is conjugated in part, probably by acetylation.

The observations suggest that the hypotheds that Dibenamine acts irreversibly on a cell receptor through the active ethylenimmonium ion may require modification.

Submitted on May 29, 1952




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Copyright © 1952 by the American Society for Pharmacology and Experimental Therapeutics.