In vitro metabolism of imipramine by brain microsomes: effects of inhibitors and exogenous cytochrome P450 reductase

Brain Research
D Sequeira, H W Strobel

Abstract

The metabolism of imipramine in the brains of rats was analyzed to study the activity of cytochrome P450 in brain microsomes. Brain microsomes were capable of metabolizing imipramine to both hydroxylated and N-demethylated products. The use of selective inhibitors of different cytochromes P450 effected varying changes in the metabolic profiles of formed metabolites consistent with the involvement of several P450 forms in imipramine metabolism. Quinidine inhibited the hydroxylation of imipramine competitively by 60% and 98% at concentrations of 10 microM and 100 microM, respectively. Ketoconazole and 7,8-benzoflavone at a concentration of 100 microM inhibited N-demethylation of imipramine by 75% and 30%, respectively, with a lower effect on imipramine hydroxylation. Results from studies on the incorporation of cytochrome P450 reductase into the brain microsomal system reveal a reductase concentration-dependent increase in imipramine metabolism and suggest that the reductase level in brain is an important factor for the study of catalytic activities in brain microsomal systems.

References

Sep 1, 1992·British Journal of Clinical Pharmacology·E Skjelbo, K Brøsen
Dec 17, 1990·Brain Research·H K AnandatheerthavaradaV Ravindranath
Feb 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·H Kodaira, S Spector
May 1, 1986·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·F P GuengerichM V Martin
Apr 1, 1972·Proceedings of the National Academy of Sciences of the United States of America·N Kinoshita, H V Gelboin
Aug 1, 1995·Journal of Neurochemistry·J Geng, H W Strobel
Oct 29, 1993·Biochemical and Biophysical Research Communications·M Komori
Apr 17, 1995·Biochemical and Biophysical Research Communications·H Kawashima, H W Strobel
Nov 1, 1993·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·P SuM Daneshtalab
May 1, 1993·Journal of Neurochemistry·H K AnandatheerthavaradaL Wecker
Mar 24, 1993·Molecular and Cellular Biochemistry·A V HodgsonH W Strobel
Nov 17, 1995·Journal of Chromatography. B, Biomedical Applications·D J Sequeira, H W Strobel

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Citations

Mar 1, 2000·Brain Research·P VoirolP Baumann
Jul 11, 2002·Brain Research. Molecular Brain Research·Shankar J ChintaVijayalakshmi Ravindranath
Feb 9, 2008·Drug Metabolism Reviews·C WoodlandJ P Fawcett
May 5, 2006·Molecular and Cellular Biochemistry·Sanjay YadavDevendra Parmar
Sep 26, 1997·Chemical Research in Toxicology·N CastagnoliK P Castagnoli

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