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INDUCTION AND INHIBITION OF THE IN VITRO Ν1-OXIDATION OF 9-BENZYLADENINE AND ISOMERIC 9-(NITROBENZYL)ADENINES

INDUCTION AND INHIBITION OF THE IN VITRO Ν1-OXIDATION OF 9-BENZYLADENINE AND ISOMERIC... INDUCTION AND INHIBITION OF THE IN VITRO Ν-OXIDATION OF 9-BENZYLADENINE AND ISOMERIC 9-(NITROBENZYL)ADENINES Ding Y. Liu1 and John W. Gorrod2* Chelsea Department University of London, 2 Toxicology Unit, John Wivenhoe Park, of Pharmacy, King 's College London, Manresa Road, London SW3 6LX, UK Tabor Laboratories, University of Essex, Colchester, Essex C04 3SQ, UK SUMMARY The present study investigated some aspects of the enzymology of the in vitro Ν'-oxidation of 9-benzyladenine (BA) and isomeric 9(nitrobenzyl)adenines (NBAs) using various potential inducers and inhibitors of cytochrome P-450 (CYP). When incubated with phenobarbital-induced rabbit hepatic microsomes, the N'-oxidation rates of BA and 9-(4-nitrobenzyl)adenine were about 6- and 2-fold higher than that of the control, respectively; while the Ν' -oxidation of 9-(2nitrobenzyl)adenine and 9-(3-nitrobenzyl)adenine was not markedly affected. In contrast, ß-naphthoflavone and Arochlor 1254 showed no inductive effects towards the N'-oxidation of any of these substrates. Using 12 typical CYP inhibitors, it was found that nifedipine (CYP3A inhibitor) and haloperidol (CYP2D inhibitor) showed significant inhibition towards the N'-oxidation of BA and NBAs. Therefore, the Nl-oxidation of BA and NBAs is probably catalysed by CYP3A and CYP2D subfamilies. Furthermore, when 9-(4-nitrobenzyl)adenine was incubated with compounds which possessed a certain chemical similarity to the adenine http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Drug Metabolism and Drug Interactions de Gruyter

INDUCTION AND INHIBITION OF THE IN VITRO Ν1-OXIDATION OF 9-BENZYLADENINE AND ISOMERIC 9-(NITROBENZYL)ADENINES

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Publisher
de Gruyter
Copyright
Copyright © 1999 by the
ISSN
2191-0162
eISSN
2191-0162
DOI
10.1515/DMDI.1999.15.2-3.141
Publisher site
See Article on Publisher Site

Abstract

INDUCTION AND INHIBITION OF THE IN VITRO Ν-OXIDATION OF 9-BENZYLADENINE AND ISOMERIC 9-(NITROBENZYL)ADENINES Ding Y. Liu1 and John W. Gorrod2* Chelsea Department University of London, 2 Toxicology Unit, John Wivenhoe Park, of Pharmacy, King 's College London, Manresa Road, London SW3 6LX, UK Tabor Laboratories, University of Essex, Colchester, Essex C04 3SQ, UK SUMMARY The present study investigated some aspects of the enzymology of the in vitro Ν'-oxidation of 9-benzyladenine (BA) and isomeric 9(nitrobenzyl)adenines (NBAs) using various potential inducers and inhibitors of cytochrome P-450 (CYP). When incubated with phenobarbital-induced rabbit hepatic microsomes, the N'-oxidation rates of BA and 9-(4-nitrobenzyl)adenine were about 6- and 2-fold higher than that of the control, respectively; while the Ν' -oxidation of 9-(2nitrobenzyl)adenine and 9-(3-nitrobenzyl)adenine was not markedly affected. In contrast, ß-naphthoflavone and Arochlor 1254 showed no inductive effects towards the N'-oxidation of any of these substrates. Using 12 typical CYP inhibitors, it was found that nifedipine (CYP3A inhibitor) and haloperidol (CYP2D inhibitor) showed significant inhibition towards the N'-oxidation of BA and NBAs. Therefore, the Nl-oxidation of BA and NBAs is probably catalysed by CYP3A and CYP2D subfamilies. Furthermore, when 9-(4-nitrobenzyl)adenine was incubated with compounds which possessed a certain chemical similarity to the adenine

Journal

Drug Metabolism and Drug Interactions – de Gruyter

Published: Sep 1, 1999

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