Interaction of butorphanol, with monoamine oxidase inhibitor, tranylcypromine

This investigation examines the possibility of interaction between tranylcypromine and butorphanol in comparison to pethidine. The LD50 of pethidine and butorphanol were determined in mice pretreated with the non-selective monoamine oxidase (MAO) inhibitor, tranylcypromine orally for 8 days or with oral saline solution. Tranylcypromine decreased the LD50 of both pethidine and butorphanol by 78% and 41%, respectively. Anesthetized rabbits with halothane pretreated with tranylcypromine or saline were given pethidine (5 mg/kg i.v.) or butorphanol (0.5, 1 and 2 mg/kg i.v.). Pethidine produced a marked increase in blood pressure in rabbits pretreated with tranylcypromine and did not affect significantly the heart rate. Butorphanol did not affect either blood pressure or heart rate at doses of 0.5 or 1 mg/kg. However, the largest dose of butorphanol (2 mg/kg) produced hypotension and tachycardia in rabbits pretreated with tranylcypromine. Neither pethidine nor butorphanol affected the temperature of anesthetized rabbits pretreated with tranylcypromine or saline.