Action of fenfluramine on monoamine stores of rat tissues

1. Fenfluramine is an anorexogenic agent used clinically because it is devoid of central stimulatory effects.2. In rats, fenfluramine causes a depletion of 5-hydroxytryptamine (5-HT) from the telencephalon + diencephalon which lasts longer than one might have expected from the biological half life of fenfluramine. The depleting effects of fenfluramine do not extend to brainstem, stomach and heart stores of 5-HT.3. Fenfluramine causes an increase in the turnover rate of tel-diencephalic 5-HT but such an acceleration could not be detected in the 5-HT stores of the brainstem.4. It is inferred that the effects of fenfluramine on brain 5-hydroxytryptamine may be related to the accumulation of a fenfluramine metabolite in 5-HT neurones.5. High doses of fenfluramine cause a depletion of catecholamine stores in brain and heart but the time course of this depletion is shorter than the depletion of brain 5-HT.