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Journal of Pharmacology And Experimental Therapeutics, Vol. 110, Issue 3, 315-326, 1954
Copyright © 1954 by American Society for Pharmacology and Experimental Therapeutics

STUDIES ON SYMPATHOMIMETIC AMINES. II. THE BIOTRANS-FORMATION AND PHYSIOLOGICAL DISPOSITION OF D-AM-PHETAMINE, D-P-HYDROXYAMPHETAMINE AND D-METH-AMPHETAMINE

Julius Axelrod 1

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

Methods for the estimation of d-amphetamine and its metabolic product d-p-hydroxyamphetamine in biological materials are described.

In the dog and rat the main route of biotransformation of d-amphetamine involves hydroxylation of the aromatic nucleus to form p-hydroxyamphetamine, an active pressor agent. Hydroxylation of amphetamine occurs to a negligible degree in the guinea pig and rabbit.

d-Amphetamine disappears slowly in the dog compared to its hydroxylated derivative, suggesting that in this species the major part of the pharmacological effect of the drug is due to the parent compound.

A major route of metabolism of d-methamphetamine in the dog involves demethylation to d-amphetamine.

d-Amphetamine is bound to plasma proteins to a negligible degree but is highly localized in most organ tissues.

Submitted on November 2, 1953




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Copyright © 1954 by the American Society for Pharmacology and Experimental Therapeutics.