Characterization of phentermine and related compounds as monoamine oxidase(MAO) inhibitors

Phentermine was shown in the 1970s to inhibit the metabolism of serotonin b y monoamine oxidase (MAO), but never was labeled as an MAO inhibitor; hence , it was widely used in combination with fenfluramine, and continues to be used, in violation of their labels, with other serotonin uptake blockers. W e examined the effects of phentermine and several other unlabeled MAO inhib itors on MAO activities in rat lung, brain, and liver, and also the interac tions of such drugs when administered together. Rat tissues were assayed fo r MAO-A and -B, using serotonin and beta-phenylethylamine as substrates. Ph entermine inhibited serotonin-metabolizing (MAO-A activity in all three tis sues with K-i values of 85-88 mu M. These potencies were similar to those o f the antidepressant MAO inhibitors iproniazid and moclobemide. When phente rmine was mixed with other unlabeled reversible MAO inhibitors (e.g. pseudo ephedrine, ephedrine, norephedrine; estradiol benzoate), the degree of MAO inhibition was additive. The cardiac valvular lesions and primary pulmonary hypertension that have been reported to be associated with fenfluramine-ph entermine use may have resulted from the intermittent concurrent blockage o f both serotonin uptake and metabolism (C) 2000 Elsevier Science Inc.