THE EFFECT OF PHENELZINE AND TRANYLCYPROMINE ON THE DEGRADATION OF MEPERIDINE

¹ Department of Pharmacology and Therapeutics and Department of Pediatrics, McGill University, Montreal 109, Quebec, Canada

The administration of meperidine to patients treated with monoamine oxidase (MAO) inhibitors can produce lethal reactions of unknown etiology. It was thought that they might be due to interference with the degradation of meperidine. Male Swiss mice were given phenelzine (40 µg/g) and tranylcypromine (5 µg/g) and kept in individual cages to avoid aggregation effects. At 1,4 and 24 hours after administration of MAO inhibitors, they were given meperidine ( 20µg/g), killed at various time intervals and the total body content of meperidine determined. Pheneizine inhibited the degradation of meperidine and in contrast to the prolonged effect of phenelzine on MAO, this effect disappeared within 24 hours. Tranylcypromine had a similar but slightly more prolonged effect. Chronic pretreatment with tranylcypromine did not increase the degree or duration of inhibition. Phenelzine reduced the LD5O of meperidine, an effect which also disappeared within 24 hours, whereas tranylcypromine had no effect on the LD5O. Inhibition of meperidine degradation by MAO inhibitors may contribute to the toxic reactions seen in man, but may not be the only mechanism involved.