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Journal of Pharmacology And Experimental Therapeutics, Vol. 132, Issue 2, 202-206, 1961
Copyright © 1961 by American Society for Pharmacology and Experimental Therapeutics

STIMULATORY EFFECT OF CHLORCYCLIZINE ON BARBITURATE METABOLISM

A. H. Conney 1, J. J. Burns 1, and I. A. Michaelson 2

1 The Wellcome Research Laboratories, Tuckahoe, New York
2 Laboratory of Chemical Pharmacology, National Heart Institute, Bethesda, Maryland, and The Research Service, Third (N.Y.U.) Medical Division, Goldwater Memorial Hospital, New York, N. Y.

Pretreatment of rats with chlorcyclizine for several days shortens the duration of action of a subsequent dose of hexobarbital, pentobarbital or zoxazolamine by increasing the activity of the liver microsomal enzymes that metabolize these drugs. Accelerated in vivo metabolism of hexobarbital was observed in chlorcyclizine-treated rats. Although pretreatment of rats with chlorcyclizine, barbital, phenobarbital or orphenadrine shortens the duration of action of hexobarbital, the duration of action of barbital was not significantly shortened. Pretreatment of rats with chlorcyclizine also increases the activity of enzyme systems in liver microsomes that N-demethylate 3 - methyl - 4 - monomethylamino-azobenzene and that metabolize reduced TPN. Removal of the pituitary gland, adrenal glands or testis did not prevent accelerated barbiturate metabolism by liver microsomes when chlorcyclizine or phenobarbital was administered.

Submitted on October 6, 1960




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R. Aston and P. Hibbeln
Induced Hypersensitivity to Barbital in the Female Rat
Science, September 22, 1967; 157(3795): 1463 - 1464.
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Copyright © 1961 by the American Society for Pharmacology and Experimental Therapeutics.