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Research ArticleArticle

Inhibition of Human Brain Type B Monoamine Oxidase by Tricyclic Psychoactive Drugs

JEROME A. ROTH
Molecular Pharmacology January 1978, 14 (1) 164-171;
JEROME A. ROTH
Department of Pharmacology and Therapeutics, State University of New York at Buffalo, Buffalo, New York 14214
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Abstract

The ability of a variety of tricyclic psychoactive drugs to inhibit human brain mitochondrial type B monoamine oxidase as measured by phenylethylamine (PEA) deamination was examined in vitro. At 50 µM all drugs tested, with the exception of chlorpromazine sulfoxide and imipramine N-oxide, inhibited this reaction between 40.8% and 78.4%. Lineweaver-Burk plots for imipramine, chlorpromazine, and chlorprothixene inhibition of PEA deamination displayed a mixed inhibition pattern when incubations were performed at normal atmospheric oxygen tension. When the oxygen concentration was elevated, inhibition of this reaction by each of the three drugs became more competitive. These results suggest that these drugs inhibit the B form of monoamine oxidase by binding to both the oxidized and reduced forms of the enzyme. Inhibition of monoamine oxidase by imipramine and desmethylimipramine increased as the pH was raised from 7.0 to 9.0, but because the ratio of the increase remained constant for the two drugs, inhibition probably was independent of the degree of ionization of the side chain aliphatic amine. It was also found that the optimal pH for human brain mitochondrial deamination of PEA shifted from 8.0 to 8.5 as the oxygen concentration was increased.

ACKNOWLEDGMENT The author wishes to thank Ms. Barbara Eddy for her excellent technical assistance during the course of this investigation.

  • Copyright © 1978 by Academic Press, Inc.

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Molecular Pharmacology
Vol. 14, Issue 1
1 Jan 1978
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Research ArticleArticle

Inhibition of Human Brain Type B Monoamine Oxidase by Tricyclic Psychoactive Drugs

JEROME A. ROTH
Molecular Pharmacology January 1, 1978, 14 (1) 164-171;

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Research ArticleArticle

Inhibition of Human Brain Type B Monoamine Oxidase by Tricyclic Psychoactive Drugs

JEROME A. ROTH
Molecular Pharmacology January 1, 1978, 14 (1) 164-171;
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