The metabolism of (R)-(-)-amphetamine by rabbit liver microsomes. Initial products.
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.
D000661:Amphetamine / Q000378:metabolism*; D000818:Animals; D003486:Cyanides / Q000494:pharmacology; D006168:Guinea Pigs; D006900:Hydroxylation; D066298:In Vitro Techniques; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D010634:Phenobarbital / Q000494:pharmacology; D011078:Polychlorinated Biphenyls / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D013482:Superoxide Dismutase / Q000494:pharmacology
D003486:Cyanides; C000939:2,4-dichloro-6-phenylphenoxyethylamine; D008748:Methylcholanthrene; D000661:Amphetamine; D011078:Polychlorinated Biphenyls; D013482:Superoxide Dismutase; D010634:Phenobarbital