The role of 5-hydroxytryptamine and noradrenaline in the hyperthermic reaction induced by pethidine in rabbits pretreated with pargyline.

1. Inhibition of 5-hydroxytryptamine (5-HT) synthesis by p-chlorphenylalanine protected rabbits pretreated with pargyline from the fatal hyperthermic reaction which occurs on the intravenous injection of pethidine.2. The development of tolerance to morphine did not protect against the fatal pargyline-pethidine hyperpyrexia. Moreover, the injection of nalorphine before or after pethidine conferred no protection.3. Pethidine evoked a hyperpyrexia in rabbits pretreated with lithium sulphate or yohimbine.4. Sodium diethyldithiocarbamate caused a fatal hyperpyrexia in rabbits pretreated with pargyline.5. It is concluded that the pargyline-pethidine hyperthermic interaction might involve the relative concentrations of 5-HT and noradrenaline in the hypothalamus.