Fuller R W, Snoddy H D
Pharmacol Biochem Behav. 1986 Feb;24(2):281-4. doi: 10.1016/0091-3057(86)90351-5.
The dextrorotatory enantiomer of fluoxetine was slightly more potent than the levorotatory enantiomer in antagonizing the depletion of brain serotonin by p-chloroamphetamine in rats. The time course of the depletion of brain serotonin at times out to 24 hr after the injection of p-chloroamphetamine was determined with or without simultaneous administration of one of the fluoxetine enantiomers. The dextrorotatory enantiomer prevented the depletion of brain serotonin at any time after p-chloroamphetamine. The levorotatory enantiomer prevented the initial depletion of brain serotonin at 2 and 4 hr, but by 8 hr brain serotonin concentration was decreased and by 24 hr the depletion of serotonin was almost as great as in rats treated with p-chloroamphetamine alone. The elevation of serum corticosterone that occurred acutely after injection of a low dose of p-chloroamphetamine was significantly antagonized by both enantiomers of fluoxetine, the dextrorotatory enantiomer being slightly more potent. In contrast, the lowering of DOPAC (3,4-dihydroxyphenylacetic acid) concentration in rat brain by p-chloroamphetamine was not antagonized by either enantiomer of fluoxetine, indicating this effect is not secondary to serotonin release by p-chloroamphetamine. The results are consistent with other evidence that both enantiomers of fluoxetine are potent inhibitors of serotonin uptake, the dextrorotatory enantiomer being longer-acting than the levorotatory enantiomer in rats.
在拮抗对氯苯丙胺引起的大鼠脑内5-羟色胺耗竭方面，氟西汀的右旋对映体比左旋对映体的效力略强。在注射对氯苯丙胺后长达24小时的时间内，测定了在同时或不同时给予氟西汀对映体之一的情况下脑内5-羟色胺的耗竭时间进程。右旋对映体能防止对氯苯丙胺后任何时间的脑内5-羟色胺耗竭。左旋对映体能防止在2小时和4小时时脑内5-羟色胺的初始耗竭，但到8小时时脑内5-羟色胺浓度下降，到24小时时5-羟色胺的耗竭几乎与仅用对氯苯丙胺处理的大鼠一样严重。注射低剂量对氯苯丙胺后急性出现的血清皮质酮升高被氟西汀的两种对映体显著拮抗，右旋对映体的效力略强。相反，对氯苯丙胺引起的大鼠脑内3,4-二羟基苯乙酸（DOPAC）浓度降低未被氟西汀的任何一种对映体拮抗，表明这种作用不是对氯苯丙胺释放5-羟色胺的继发效应。这些结果与其他证据一致，即氟西汀的两种对映体都是5-羟色胺摄取的有效抑制剂，在大鼠中右旋对映体的作用时间比左旋对映体长。
