Abstract

Tranylcypromine and meperidine administered four hours apart to mice in a ratio of 3:10 by weight exhibited marked superadditivity of their toxic actions, the LD50 of the combination being only 0.54 of that which would be expected on the basis of their individual toxicities. Pretreatment with p-chlorophenylalanine (100 mg/kg) at 72, 48 and 24 hours before the experiment markedly lowered the mortality of mice receiving tranylcypromine and meperidine in a 3:10 ratio four hours apart but not those receiving either tranyleypromine or meperidine alone. Intertreatment with doses of 5-hydroxytryptophan as low as 5 mg/kg one hour before meperidine administration markedly increased mortality of mice receiving the tranylcypromine-meperidine combination. Thus the toxic response of mice to the tranylcypromine-meperidine combination may be mediated by 5-hydroxytryptamine. Meperidine administration four hours after tranylcypromine resulted in a marked hyperthermic response. This response was significantly augmented if 5-hydroxytryptophan was coadministered with the meperidine. Pretreatment with p-chlorophenylalanine did not prevent the development of a hyperthermic response to meperidine in mice administered tranylcypromine four hours earlier; however, the p-chlorophenylalanine-pretreated mice had generally lower body temperatures than control mice.