Cilobamine , an
antidepressant, was investigated for its influence on the hepatic
drug metabolizing
enzymes ( DME ) of male Charles River CD rats.
Cilobamine doses (3, 10, 30, 100, and 300 mg/kg po, as free base) were compared to
sodium phenobarbital (PB) doses (3, 10, 30, 100, and 200 mg/kg po, as free
acid). Compounds were given daily for 4 days and all tests were done on Day 5.
Ethylmorphine n-demethylase,
aniline hydroxylase, microsomal
cytochrome P-450 content, relative liver weight, and recoverable microsomal
protein were quantitated. The results indicated that
cilobamine was an inducer of the DME but not as potent as PB.
Cilobamine did not exert any inductive responses at 3 mg/kg.
At 10 and 30 mg/kg some but not all test systems were increased. However, at 100 and 300 mg/kg all were increased. PB increased all systems at all doses studied. Electron micrographs of livers of rats given 100 mg/kg of
cilobamine or PB revealed
hypertrophy of the smooth endoplasmic reticulum. The time course of induction in rats given 100 mg/kg po showed that responses in the
cilobamine rats peaked after the second dose and plateaued with later doses. Responses in PB rats increased markedly after one dose and showed a continual increase with later doses. Induction of the DME was also demonstrated in female rats.