Article date: April 1975
By: W. BUCZKO, G. GAETANO, S. GARATTINI in Volume 53, Issue 4, pages 563-568
(+)‐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 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).
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.
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.
(+)‐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 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).
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.
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.
DOI: 10.1111/j.1476-5381.1975.tb07395.x
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