INCREASE OF PENTOBARBITONE METABOLISM INDUCED IN RATS PRETREATED WITH SOME CENTRALLY ACTING COMPOUNDS

Abstract

Rats treated with phenobarbitone, phenaglycodol, glutethimide, nikethamide, meprobamate, chlorbutol and chlorpromazine showed an increased metabolism of pentobarbitone and, at the same time, a diminished sleeping-time after pentobarbitone. This effect developed 24 hr after treatment, the maximum increase in metabolism occurring after about 48 hr. The increased pentobarbitone metabolism was inhibited by ethionine injected shortly before treatment. Using a liver slice preparation, increased pentobarbitone metabolism was also observed in vitro. These results are in accord with the view that the capacity of compounds to increase pentobarbitone metabolism may be related to their ability to act directly on microsomal enzyme systems.