ENHANCEMENT IN VIVO OF DRUG OXIDATIONS FOLLOWING ADMINISTRATION OF BENZPHETAMINE, ACETONE, METYRAPONE AND DIMETHYLSULFOXIDE

Abstract

Effects of benzphetamine, acetone, metyrapone and dimethylsulfoxide administration to rats on the metabolism of drugs by liver 9,000 .times. g supernatant fraction were studied. Activities for aniline hydroxylation and phenacetin O-deethylation were increased while ethylmorphine and benzphetamine N-demethylations were unchanged by the single administration of acetone, metyrapone or dimethylsulfoxide. Increase in aniline hydroxylase activity by about 53.4% and in phenacetin O-deethylase activity by about 44.4% were observed at 30 min after the single administration of benzphetamine whereas ethylmorphine N-demethylase activity was slightly decreased. NADPH-cytochrome P-450 reductase activity and cytochrome P-450 content were unaltered until 12 h after the single administration of benzphetamine. Aniline hydroxylation was increased by the addition of benzphetamine to the incubation mixture and the increase in aniline hydroxylation caused by benzphetamine could be reversed by washing the microsomes.