Wong D T, Reid L R, Threlkeld P G
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285.
Pharmacol Biochem Behav. 1988 Oct;31(2):475-9. doi: 10.1016/0091-3057(88)90376-0.
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.
氟西汀的R-和S-对映体降低了进食大鼠和2-脱氧葡萄糖诱导的食欲亢进大鼠的食物摄入量。在这两种喂养模式中，S-对映体的效力略强。氟西汀的两种对映体产生厌食作用的效力与其作为体内5-羟色胺（5HT）摄取抑制剂的效力相当。两种对映体在体外均为5HT摄取的选择性抑制剂，对大鼠脑中的5HT-1、5HT-1A和5HT-2受体或其他受体仅表现出微弱的亲和力。氟西汀对进食大鼠的厌食作用不会被中枢或外周作用的5HT-2受体拮抗剂（利坦色林、LY53857、二甲苯脒、BW 501C67）或非特异性5HT受体拮抗剂麦角苄酯逆转。然而，文中讨论了氟西汀厌食作用所涉及的5-羟色胺能机制。
