Phentermine and other monoamine-oxidase inhibitors may increase plasma serotonin when given with fenfluramines

Abstract

1It was suggested that these findings, were due to an increase in circulating serotonin. Subsequently, the US Food and Drug Administration found heart-valve lesions among patients taking a fenfluramine without phentermine. Given the paucity of data on phentermine’s actions, we determined whether phentermine could modify the metabolism of other monoamines besides the norepinephrine released from sympathetic neurons. In rats, phentermine, like d-amphetamine, releases dopamine into brain synapses. 2 We tested the ability of a low dose (15 mg by mouth) to affect plasma dopamine in human beings. Nine young, non-obese male volunteers gave blood just before, and 1, 2, or 4 h after receiving the drug. Plasma dopamine concentrations, assayed by radioimmunoassay 3 , rose with phentermine (p<0·05; ANOVA; Wilcoxon’s test); however a greater increase was noted in serotin levels within the blood platelets as assayed by ELISA and confirmed by high performance liquid chromatography (r=0·496; p<0·001). The increase in platelet serotonin could reflect increased release of serotonin from enterochromaffin cells, or inhibition of its metabolism by monoamine oxidase (MAO). That the increase resulted from MAO inhibition and not from increased serotonin release was shown by the finding that plasma serotonin concentration fell slightly. That phentermine inhibits the MAO which catabolises serotonin was well known in the early 1970s,