Effect of Nonselective and Selective Inhibitors of Monoamine Oxidases A and B on Pethidine Toxicity in Mice

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1984 May 1

PMID 6428496

Citations 4

Authors

R Boden

R Botting

P Coulson

G Spanswick

Affiliations

Soon will be listed here.

Abstract

The LD50 of pethidine was determined in mice pretreated (4 h) either with the nonselective monoamine oxidase (MAO) inhibitor, phenelzine or with clorgyline, a selective inhibitor of MAO A or deprenyl, a selective inhibitor of MAO B. Phenelzine or combined clorgyline plus deprenyl pretreatments decreased pethidine LD50. Clorgyline or deprenyl alone did not affect pethidine toxicity. Whole brain 5-hydroxytryptamine (5-HT) concentrations were measured in the pretreated mice. 5-HT levels were approximately doubled (P less than 0.001) after phenelzine or clorgyline plus deprenyl treatment, but not after clorgyline or deprenyl given alone. These results indicate that both MAO A and MAO B need to be inhibited to increase pethidine toxicity and brain 5-HT levels. They support the involvement of 5-HT in the toxic interaction between pethidine and MAO inhibitors.

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