Effects of mazindol, fenfluramine and chlorimipramine on the 5-hydroxytryptamine uptake and storage mechanisms in rat brain: similarities and differences.
Mazindol and fenfluramine inhibited in vitro the uptake of 5-HT into rat forebrain synaptosomes, whether the synpatosomes were incubated in vitro with the drugs or obtained from animals pretreated in vitro. Chlorimipramine was also effective in this latter preparation. Dose-response relationships and time course of this effect for the various drugs were determined. Fenfluramine also caused release of 5-HT from preloaded synaptosomes in in vitro incubations. Mazindol did not. Brain 5-HT levels were measured after acute and chronic administration of mazindol, fenfluramine and chlorimipramine. Mazindol had no effect, fenfluramine was active in reducing brain 5-HT concentrations acutely and chlorimipramine only after chronic administration. Therefore, it seems that even a long lasting inhibition of the uptake, such as that induced by mazindol, is not sufficient, per se, to cause depletion of brain 5-HT.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002997:Clomipramine / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology; D003984:Dibenzazepines / Q000494:pharmacology*; D005277:Fenfluramine / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008454:Mazindol / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism; D013997:Time Factors
D003984:Dibenzazepines; D007211:Indoles; D005277:Fenfluramine; D012701:Serotonin; D008454:Mazindol; D002997:Clomipramine; D003913:Dextroamphetamine