THE FATE OF DIBENZYLINE IN THE BODY AND THE ROLE OF FAT IN ITS DURATION OF ACTION

¹ Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Public Health Service, U. S. Department of Health, Education, and Welfare, Bethesda, Maryland
² Department of Pharmacology, Harvard Medical School, Boston, Mass.

Methods are described for the estimation of Dibenzyline and its metabolite, N-phenoxyisopropyl-N-benzyl amine, in biological material.

After intravenous administration in the dog, Dibenzyline is in part rapidly metabolized and in part localized in fat where it is stable and from which it slowly diffuses into the bloodstream. The degree of adrenergic blocking activity is related to the concentration of the drug in fat. Studies with C¹⁴ labelled Dibenzyline show that there are definite though small concentrations of drug in plasma during the time that the effects of the drug are exerted.

After oral administration about four times as much Diberizyline as Dibenamine is found in body fat. The oral efficacy of Dibenzyline may be related to its high fat solubility.

A major pathway of biotransformation of Dibenzyline involves dealkylation to yield N-phenoxyisopropyl-N-benzyl amine. No evidence that Dibenzyline is hydrolyzed in vivo to yield the corresponding alcohol was found.

The observations presented in this paper suggest that it is unnecessary to postulate that Dibenzyline and other adrenergic blocking agents of the Dibenamine type act irreversibly on a cell receptor.

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