Effect of nonselective and selective inhibitors of monoamine oxidases A and B on pethidine toxicity in mice.
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.
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003010:Clorgyline / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D008614:Meperidine / Q000633:toxicity*; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D012642:Selegiline / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism
D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D012701:Serotonin; D008614:Meperidine; D003010:Clorgyline