Abstract
Four phenothiazine derivatives were compared with respect to the extent that they stimulated hepatic microsomal drug metabolism of mature male rats. Daily oral administration of chlorpromazine (16 mg/kg) for 3 days stimulated ethylmorphine N-demethylase activity to 135% of control values, Three- and seven-day pretreatment with promazine, thioridazine, or triflupromazine, and 7-day pretreatment with chlorpromazine stimulated ethylmorphine N-demethylase activity less than observed for 3-day chlorpromazine pretreatment. Administration of chlorpromazine (32 mg/kg) or of promazine (64 mg/kg) for 3 days stimulated both aniline hydroxylase activity and cytochrome P-450 content to levels exceeding 150% of control values. After 7 days of chlorpromazine or promazine administration, aniline hydroxylase activity declined, whereas cytochrome P-450 content was maintained or increased. After 7 days of pretreatment with thioridazine or triflupromazine, aniline hydroxylase activity and cytochrome P-450 content were weakly stimulated.
Footnotes
- Received July 1, 1974.
- Copyright © 1974 by The American Society for Pharmacology and Experimental Therapeutics
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