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Journal of Pharmacology And Experimental Therapeutics, Vol. 175, Issue 2, 311-317, 1970
Copyright © 1970 by American Society for Pharmacology and Experimental Therapeutics

INDUCTION OF HEPATIC DRUG METABOLISM IN RATS BY METHYLCHLOROFORM INHALATION

GEORGE C. FULLER 1, ARNOLD OLSHAN 1, SURENDRA K. PURI 1, and HARBANS LAL 1

1 Department of Pharmacology and Toxicology, University of Rhode Island, Kingston, Rhode Island

Inhalation of methylchloroform (2500-3000 ppm) for 24 hours decreased the duration of action of hexobarbital, meprobamate and zoxazolamine. This was accompanied by an increase in the metabolism of hexobarbital, zoxazolamine and aminopyrine in vitro by hepatic microsomal enzymes. CO-binding pigment (cytochrome p-450 reduced) and nicotinainide adenine dinucleotide phosphate cytochrome c reductase activity of hepatic microsomal fractions were increased. Pretreatment of rats with cycloheximide or actinomycin D prevented the methylchloroform-induced decrease in the hexobarbital narcosis and the increase in hepatic drug metabolism. Repeated injections of morphine or adrenalectomy did not block methylchloroform effects. Immediately after 24 hour of methylchloroform inhalation the methylchloroform concentration in liver was markedly greater than that in the blood.

Submitted on November 13, 1969
Accepted on July 14, 1970




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Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics.