Fluoxetine at anorectic doses does not have properties of a dopamine uptake inhibitor.
Although fluoxetine is a highly selective inhibitor of serotonin uptake in vitro and in vivo, some investigators have suggested that dopamine uptake inhibition may contribute to anorectic actions of fluoxetine. The present experiments were done to determine fluoxetine's effects in some animal protocols in which dopamine uptake inhibitors have characteristic actions. Mazindol prevented the depletion of striatal dopamine and its metabolites by amphetamine in iprindole-pretreated rats, but fluoxetine had no effect. Mazindol prevented the depletion of striatal dopamine and its metabolites by 6-hydroxydopamine injected intracerebroventricularly into rats, but fluoxetine had no effect. Mazindol enhanced the elevation of 3,4-dihydroxyphenylacetic acid concentration in rat brain after spiperone injection, but fluoxetine did not cause that effect. Fluoxetine did not mimic amfonelic acid in antagonizing the retention of alpha-methyl-m-tyramine invant striatum after the injection of alpha-methyl-m-tyrosine. These results show that fluoxetine, at doses that are effective in blocking the serotonin uptake carrier and causing anorexia, does not block the dopamine uptake carrier.
Fuller
R W
RW
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN.
Hemrick-Luecke
S K
SK
Snoddy
H D
HD
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000661:Amphetamine / Q000037:antagonists & inhibitors; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D008454:Mazindol / Q000494:pharmacology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley
D001067:Appetite Depressants; D018765:Dopamine Uptake Inhibitors; D005473:Fluoxetine; D015102:3,4-Dihydroxyphenylacetic Acid; D016627:Oxidopamine; D008454:Mazindol; D000661:Amphetamine; D004298:Dopamine; D006719:Homovanillic Acid