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Molecular Pharmacology

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Research ArticleArticle

Inhibition of Drug Metabolism

III. Inhibition of Hexobarbital Metabolism in the Intact Rat and in the Isolated Perfused Liver by 2-Diethylaminoethyl 2,2-Diphenylvalerate HCl (SKF 525-A) and Its N-Deethylated Derivatives

R. E. STITZEL, M. W. ANDERS and G. J. MANNERING
Molecular Pharmacology July 1966, 2 (4) 335-340;
R. E. STITZEL
Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455
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M. W. ANDERS
Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455
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G. J. MANNERING
Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455
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Abstract

SKF 525-A and its secondary and primary amine analogs, 2-ethylaminoethyl 2,2-diphenylvalerate HCl (SKF 8742-A) and 2-aminoethyl 2,2-diphenylvalerate HBr (AEDV), were compared for their effects on (a) the rate of hexobarbital metabolism in the intact rat, (b) hexobarbital sleeping time, and (c) rate of hexobarbital metabolism by the isolated perfused liver. The three compounds were found to be equipotent inhibitors by all three measurements. However, when the time interval between the injections of the inhibitor and the hexobarbital was increased from 45 min to 5 hr, SKF 525-A prolonged sleeping time longer than SKF 8742-A, and SKF 8742-A was more effective than AEDV. These results are interpreted to support the view that N-dealkylation plays an important role in the inhibition of drug metabolism by SKF 525-A.

ACKNOWLEDGMENT This research was supported by USPHS grant No. GM-12543. Part of this material appears in abstract form in The Pharmacologist 7, 159 (1965). The authors gratefully acknowledge the able technical assistance of Mrs. Shirley Green.

  • Copyright ©, 1966, by Academic Press Inc.

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Molecular Pharmacology
Vol. 2, Issue 4
1 Jul 1966
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Research ArticleArticle

Inhibition of Drug Metabolism

R. E. STITZEL, M. W. ANDERS and G. J. MANNERING
Molecular Pharmacology July 1, 1966, 2 (4) 335-340;

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Research ArticleArticle

Inhibition of Drug Metabolism

R. E. STITZEL, M. W. ANDERS and G. J. MANNERING
Molecular Pharmacology July 1, 1966, 2 (4) 335-340;
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