Inhibition of the microsomal N-hydroxylation of 2-amino-6-nitrotoluene by a metabolite of methimazole

doi:10.1016/0006-291X(83)91744-8

Biochemical and Biophysical Research Communications

Volume 113, Issue 2, 15 June 1983, Pages 433-438

https://doi.org/10.1016/0006-291X(83)91744-8 Get rights and content

Abstract

Inhibition studies were used to investigate the identity of the microsomal enzyme(s) responsible for the NADPH-dependent N-hydroxylation of 2-amino-6-nitrotoluene. The N-hydroxylation reaction was inhibited by several cytochrome P-450 inhibitors as well as by methimazole, a substrate for flavin-containing monooxygenase. Heat inactivation of flavin-containing monooxygenase had no effect on the rate of the reaction but abolished the inhibition by methimazole. These results indicate that the flavin-containing monooxygenase-mediated metabolism of methimazole produced an inhibitor of the cytochrome P-450-catalyzed N-hydroxylation reaction. When glutathione was included in the incubation the inhibition by methimazole was abolished, presumably due to the reduction of oxygenated metabolites of methimazole. These results show that methimazole inhibition does not necessarily implicate flavin-containing monooxygenase in microsomal N-hydroxylation reactions.

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Inhibition of the microsomal N-hydroxylation of 2-amino-6-nitrotoluene by a metabolite of methimazole

Abstract

Chem. Biol. Interact

Biochem. Pharmacol

Biochem. Pharmacol

J. Biol. Chem

Biochem. Pharmacol

Pharmacol. Rev

Drug Metab. Disp

Xenobiotica

Cancer Res