The serotonergic appetite suppressant fenfluramine. Reappraisal and rejection

Medical and social pressures have led to increased emphasis on dieting. However, there has been a concurrent world wide increase of obesity. Therefore, much attention has been paid to the development of drugs which decrease appetite. The most extensively used drug of this type over the past three decades has been the serotonergic compound fenfluramine. Recent findings have cast doubt on the previously accepted view that its action requires the release of central 5-HT. Instead, it seems likely that action on specific 5-HT receptors independently of 5-HT stores is involved. It is ironic that these new developments in understanding its mechanism of action have coincided with the recognition of its cardiovascular side-effect apparent especially in patients treated with d-fenfluramine combined with phentermine. This has forced the withdrawal of fenfluramine (both as racemate and d-isomer) from clinical use. The implications of these developments are commented upon.