Effect of fenfluramine on 5 hydroxytryptamine uptake and release by rat blood platelets

(+) Fenfluramine reduces the central stores of 5 hydroxytryptamine (5 HT) by a poorly understood mechanism. Rat blood platelets have been used in this study as a simple model for serotoninergic nerve endings. (+) Fenfluramine shows a dual effect: it inhibits the uptake of [¹⁴C] 5 HT by platelets and it releases newly absorbed [¹⁴C] 5 HT from platelets. The inhibition of [¹⁴C] 5 HT uptake induced by (+) fenfluramine appears very rapidly, is concentration dependent and seems not to be competitive. (+) Fenfluramine is 10 times less effective than chloroimipramine but 10 times more effective than (+) amphetamine; (+) fenfluramine is more active than its (-) isomer or its metabolite nonfenfluramine ((+) or (-) form). The release of [¹⁴C] 5 HR from platelets induced by (+) fenfluramine is concentration dependent but increases with increased incubation time. Both chloroimipramine and (+) amphetamine are in comparison very poor release inducers; (+) fenfluramine is more active than its (-) isomer or its metabolites. The effect on [¹⁴C] 5 HT uptake exerted by (+) fenfluramine and chloroimipramine in vitro could not be observed in vivo. The observed effect of fenfluramine on the uptake and release of 5 HT may explain the lowering action of fenfluramine on the brain 5 HT level, an effect considered of importance for the anorectic effect of this drug.