Role of brain monoamines in the fatal hyperthermia induced by pethidine or imipramine in rabbits pretreated with a monoamine oxidase inhibitor.
1. The intravenous infusion of pethidine or imipramine, in doses of 5 mg/kg, caused fatal hyperpyrexia in rabbits premedicated with pargyline.2. The drug interaction was not antagonized when either reserpine or alpha-methyl-p-tyrosine were administered with pargyline. Neither reserpine nor alpha-methyl-p-tyrosine prevented the rise in brain stem 5-hydroxytryptamine content following monoamine oxidase inhibition, although the increase in catecholamines normally produced by pargyline was prevented.3. The development of fatal hyperthermia was completely prevented when rabbits were treated with p-chlorophenylalanine prior to pargyline premedication. In these animals, the concentration of brain stem catecholamines, but not 5-hydroxytryptamine, was increased.4. The results indicate that the hyperthermia evoked by pethidine or imipramine in combination with monoamine oxidase inhibitors can take place only in the presence of raised concentrations of 5-hydroxytryptamine in the brain stem.
D000588:Amines / Q000378:metabolism*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001923:Brain Chemistry; D001933:Brain Stem / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D010134:Fenclonine / Q000494:pharmacology; D006955:Hypernatremia / Q000139:chemically induced*; D007099:Imipramine; D008297:Male; D008614:Meperidine; D008781:Methyltyrosines / Q000494:pharmacology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D010293:Pargyline / Q000494:pharmacology; D011817:Rabbits; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors
D000588:Amines; D008781:Methyltyrosines; D008996:Monoamine Oxidase Inhibitors; D012701:Serotonin; D012110:Reserpine; D008614:Meperidine; D010293:Pargyline; D007099:Imipramine; D010134:Fenclonine; D004298:Dopamine; D009638:Norepinephrine