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.