Suppression of food intake in rats by fluoxetine: comparison of enantiomers and effects of serotonin antagonists.
R- and S-enantiomers of fluoxetine lowered food intake in meal-fed rats and in 2-deoxyglucose-induced hyperphagic rats. In both feeding paradigms, the S-enantiomer was slightly more potent. The potency of the two enantiomers of fluoxetine in producing anorectic effects paralleled their potency as inhibitors of 5-hydroxytryptamine (5HT) uptake in vivo. Both enantiomers were selective inhibitors of 5HT uptake in vitro and showed only weak affinity for 5HT-1, 5HT-1A and 5HT-2 receptors or for other receptors in rat brain. The anorectic effect of fluoxetine in meal-fed rats was not reversed by either centrally or peripherally acting 5HT-2 receptor antagonists (ritanserin, LY53857, xylamidine, BW 501C67) or a nonspecific 5HT receptor antagonist, metergoline. However, the serotonergic mechanism involved in the anorexic effect of fluoxetine is discussed.
Wong
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Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285.
Reid
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LR
Threlkeld
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PG
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology*; D007536:Isomerism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology*
D015306:Biogenic Monoamines; D012702:Serotonin Antagonists; D005473:Fluoxetine; D003847:Deoxyglucose