Some effects of mazindol, an anorectic drug, on rat brain monoaminergic systems.
Mazindol was devoid of effect both on rat brain steady state levels of 5-HT, 5-HIAA and tryptophan and on the rate of synthesis of 5-HT in the rat brain. Mazindol had no effect on rat brain 5-HT uptake in vivo as determined by the effect of drug pretreatment on the ability of p-chloroamphetamine to lower central 5-HT levels. A large dose of mazindol caused a slight transient decrease in rat brain levels of NA and DA. Blockade of rat brain catecholamine uptake was quantified by studying drug effects on the ability of intraventricularly administered 6-hydroxydopamine to lower brain NA and DA content. Mazindol was an extremely potent inhibitor of rat brain NA uptake in vivo, being 4-5 times more potent than desipramine. Mazindol also blocked rat brain DA uptake. Doses of mazindol needed to release alpha-methyl-m-tyramine from the rat striatum were appreciably greater than the corresponding doses of d-amphetamine. The neurochemical profile of mazindol bears a much closer resemblance to that of d-amphetamine than to that of fenfluramine.
D000818:Animals; D001679:Biogenic Amines / Q000032:analysis*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D003342:Corpus Striatum / Q000032:analysis; D004298:Dopamine / Q000032:analysis; D004347:Drug Interactions; D006892:Hydroxydopamines / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008454:Mazindol / Q000494:pharmacology*; D009638:Norepinephrine / Q000032:analysis; D051381:Rats; D012701:Serotonin / Q000032:analysis / Q000096:biosynthesis; D014364:Tryptophan / Q000032:analysis; D010133:p-Chloroamphetamine / Q000494:pharmacology; D010136:p-Hydroxyamphetamine / Q000032:analysis
D001679:Biogenic Amines; D006892:Hydroxydopamines; D007211:Indoles; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D010133:p-Chloroamphetamine; D014364:Tryptophan; D008454:Mazindol; D010136:p-Hydroxyamphetamine; D004298:Dopamine; D009638:Norepinephrine