EFFECT OF FENFLURAMINE ON 5‐HYDROXYTRYPTAMINE UPTAKE AND RELEASE BY RAT BLOOD PLATELETS

Abstract

1 (+)-Fenfluramine reduces the central stores of 5-hydroxytryptamine (5-HT) by a poorly understood mechanism. 2 Rat blood platelets have been used in this study as a simple model for serotoninergic nerve endings. 3 (+)-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. 4 The inhibition of [¹⁴C]-5-HT uptake induced by (+)-fenfluramine appears very rapidly, is concentration-dependent and seems not to be competitive. (+)-Fenfluramine is ten times less effective than chloroimipramine but ten times more effective than (+)-amphetamine; (+)-fenfluramine is more active than its (-)-isomer or its metabolite norfenfluramine ((+)- or (-)-form). 5 The release of [¹⁴C]-5-HT 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. 6 The effect on [¹⁴C]-5-HT uptake exerted by (+)-fenfluramine and chloroimipramine in vitro could not be observed in vivo. 7 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.