Biopharmaceutical Studies on Neuroleptic Butyrophenones. V. Effects of Chronic Treatment on Adrenal and Hepatic Drug-Metabolizing Enzyme System in Rats

Abstract

The effects of clofluperol (CLO) and haloperidol (HAL) on the adrenal and hepatic drug-metabolizing enzyme system were studied after oral administration to rats for 1 and 2 weeks. Ten mg/kg of both drugs inhibited animal growth, decreased liver weights and elevated plasma corticosterone levels. CLO, but not HAL, caused pronounced enlargement of the adrenals, the size of which increased with increasing the adrenal CLO contents. Treatment with both drugs led to a decrease in the activities of aminopyrine (AM) N-demethylase and aniline (AN) hydroxylase in liver 9000×g supernatant fraction, decreased liver microsomal cytochrome P-450 levels and reduced the spectral changes of cytochrome P-450 induced by AM or AN. The duration of sleep induced by hexobarbital was prolonged by treatment with both drugs. When CLO (10 mg/kg) was dosed for 2 weeks, the sleep times were extremely protracted.