The metabolism of (R)-(-)-amphetamine by rabbit liver microsomes. Initial products

VM Florence, EW Di Stefano, CY Sum and AK Cho

The metabolism of 1-amphetamine in rabbit liver is complex in that several routes may give rise to the same intermediate. In this study, the subsequent metabolism of the primary products of N- and C-oxidation were blocked by selecting appropriate incubation conditions. The resulting simplified system was used to investigate the enzymes involved in the two pathways. Phenobarbital treatment increased N- and C-hydroxylation, whereas 3-methylcholanthrene treatment had an inhibitory effect on both pathways. Inhibitors of cytochrome P-450 were either nonselective or were partially selective in inhibiting the two routes of amphetamine metabolism. Induction modulated the sensitivity toward the inhibitors of N- and C-oxidation.

Volume 10, Issue 4, pp. 312-315, 07/01/1982
Copyright © 1982 by American Society for Pharmacology and Experimental Therapeutics

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