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Effects of Chlorpromazine and Phenobarbital on Rat Liver and Brain Oxidative N‐Oxidase and N‐Demethylase Activities

Effects of acute and chronic treatment of rats with chlorpromazine (CP) and phenobarbital respectively on the N‐oxidase and the N‐demethylase activities of liver and brain were studied. The acute treatment with CP caused a reduction in body weight, but no change in liver weight. The measured enzyme activities of liver homogenates decreased by 12–19 per cent compared with controls. These decreases were not statistically significant in every age group, but tended to be comparatively marked accompanied with aging. Phenobarbital produced no significant change in body weights, but brought about slight enlargement of the liver, and caused induction of the enzyme activities. On daily treatment with CP, the body weights went back their initial whights by seven days, and the activities in liver homogenates were restored to almost the same level as those of controls or slightly higher. Weights of the liver and brain did not change. The enzyme activities of the brain were neglisibly low and showed no change either by treatment with CP or phenobarbital. These data may suggest the possibility that when CP is medicated in patients, its plasma level might increase initially and then decrease gradually during medication, following the changes of its metabolizing enzyme activities.