The Metabolism of Amphetaminein vitroby Rabbit Liver Preparations: A Comparison ofR(−) andS(+) Enantiomers

Abstract

Incubation of R(-), S(+) and R-S(.+-.) amphetamines with rabbit liver supernatant indicated that R(-) was metabolized at a faster rate than S(+), but that racemic amphetamine was metabolized at the same rate as S(+) during 1 h incubations. N-Hydroxyamphetamine and 1-phenyl-2-propanol were the major compounds detected in both R(-) and S(+) amphetamine incubations. Phenylacetone oxime was detected in significant quantities after 3 h incubations of R(-) amphetamine, but only in minor quantities from S(+). A fall in the amount of N-hydroxyamphetamine present in R(-) amphetamine incubations after a 3 h period as compared to a 1 h incubation, paralleled by a rise in the amount of phenylacetone oxime during 3 h suggested that the oxime was derived as a secondary metabolite from N-hydroxyamphetamine. R(-) and S(+) N-hydroxyamphetamines were both metabolized to phenylacetone oxime by rabbit liver supernatant, but the R(-) enantiomer was converted at a faster rate than S(+).