MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by ANDERS, M. W.
Right arrow Articles by MANNERING, G. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by ANDERS, M. W.
Right arrow Articles by MANNERING, G. J.

Molecular Pharmacology, Vol 2, 341-346, Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics

Inhibition of Drug Metabolism

IV. Induction of Drug Metabolism by 2-Diethylaminoethyl 2,2-Diphenylvalerate HCl(SKF 525-A) and 2,4-Dichloro-6-phenylphenoxyethyldiethylamine HBr (Lilly 18947) and the Effect of Induction on the Inhibitory Properties of SKF 525-A Type Compounds

M. W. ANDERS 1 and G. J. MANNERING 1

1 Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455

The chronic administration (5 days) of SKF 525-A and Lilly 18947 to rats induced increased microsomal enzyme activity as measured by the N-dealkylation of these compounds themselves as well as that of ethylmorphine. In rats whose rates of hexobarbital metabolism had been increased as a result of the repeated administration of SKF 525-A, hexobarbital metabolism was still inhibited when a final dose of SKF 525-A was given. Similarly, in phenobarbital treated rats, SKF 525-A, its product of N-dealkylation, 2-ethylaminoethyl 2,2-diphenylvalerate HCl (SKF 8742-A), and its primary amine analog, 2-aminoethyl 2,2-diphenylvalerate HBr (AEDV), were all effective inhibitors of the enhanced rate of hexobarbital metabolism. These results are explained on the basis that the inductive process involves the synthesis of new enzymic protein that is as readily inhibited by SKF 525-A type compounds as that which was present before induction. Even though the rate of metabolism of SKF 525-A is increased as a result of induction it continues to exert its effects through its products of N-dealkylation, which are also excellent inhibitors.

Note:
ACKNOWLEDGMENTS This research was supported by USPHS grant No. GM-12543. Part of this material appears in abstract form in Federation Proc. 23, 537 (1964) and in a thesis by M. W. Anders in partial fulfillment of the requirements for the Ph.D. degree in the Department of Pharmacology, University of Minnesota, 1964. The authors gratefully acknowledge the able technical assistance of Mrs. Sheila Ham and Mrs. Margaret (Chang) Lu.

Submitted on February 17, 1966




This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
M. F. Grubb, S. Diamond, and D. D. Christ
In Vitro and In Vivo Effects of the Arylamine Human Immunodeficiency Virus Protease Inhibitor 4R-(4alpha ,5alpha ,6beta ,7beta )-1-[(3-(1-Imidazoylcarbamoyl)phenyl)methyl]-3-[(3-aminophenyl)methyl]hexahydro-5,6-dihydroxy-4,7-bis(phenylmethyl)-2H-1,3-diazepin-2-one (SD894) on Rat Hepatic Cytochrome P450 2B and 3A
Drug Metab. Dispos., December 1, 1997; 25(12): 1424 - 1428.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics