1. The metabolism in vitro and microsomal interactions of (+)-amphetamine, (−)-amphetamine, (+)-benzphetamine and (−)-benzphetamine were studied with hepatic microsomes from phenobarbitone-pretreated male rabbits. 2. (+)-Benzphetamine was N-demethylated 30–35% faster than (−)-benzphetamine, but the apparent Michaelis constants for the two enantiomers were similar. 3. (−)-Amphetamine was deaminated about 200% faster than (+)-amphetamine. 4. The benzphetamine enantiomers gave qualitatively and quantitatively identical type I microsomal difference spectra (peak, 390nm; trough, 425nm) indicating identical apparent binding affinities for microsomes and identical spectral changes at maxima (ΔEmax. values). 5. The amphetamine enantiomers gave qualitatively identical type II microsomal difference spectra (peak, 433nm; trough, 395nm). However, the type II spectral data indicated that (+)-amphetamine had a markedly higher apparent binding affinity than (−)-amphetamine for microsomes. The amphetamine enantiomers gave identical ΔEmax. values. 6. The benzphetamine enantiomers (0.5mm) enhanced the rate of microsomal cytochrome P-450 reduction by NADPH by 400–500%, (+)-benzphetamine enhancing the rate 20–25% more than (−)-benzphetamine. 7. The amphetamine enantiomers decreased the rate of microsomal cytochrome P-450 reduction by NADPH. At a concentration of 2mm, (+)-amphetamine decreased the rate more than (−)-amphetamine. 7. All four enantiomers enhanced microsomal NADPH oxidation.

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