Fuller R W, Wong D T, Robertson D W
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
Med Res Rev. 1991 Jan;11(1):17-34. doi: 10.1002/med.2610110103.
In summary, fluoxetine is a highly selective serotonin uptake inhibitor in vitro and in vivo. The conformation of fluoxetine, which resembles that of sertraline and other serotonin uptake inhibitors, appears to be a key feature that enables its high affinity and selective interaction with the serotonin transporter. The para-trifluoromethyl substituent, however, is also a pivotal structural element. The molecular pharmacology of fluoxetine has been well-defined, and its in vivo pharmacological effects appear to be mediated almost exclusively by serotonin uptake inhibition. Its selectivity for the serotonin transporter, lack of affinity for neurotransmitter receptors, and retention of selectivity following metabolism to norfluoxetine make fluoxetine a useful tool to explore pharmacologically induced increases in serotonin neurotransmission. Fluoxetine has found a variety of therapeutic application. Its use in treating depression has been most extensively studied, but controlled clinical studies also suggest the drug may have a role in treating obesity and bulimia. Moreover, a variety of other psychiatric disorders may be treatable with this drug. Regardless of the outcome of these clinical trials, it is apparent that fluoxetine has found a useful niche in therapy, and can be used as a probe to determine the role of serotonin in modulating human pathophysiologies.
总之，氟西汀在体外和体内均是一种高度选择性的5-羟色胺摄取抑制剂。氟西汀的构象与舍曲林及其他5-羟色胺摄取抑制剂的构象相似，这似乎是使其与5-羟色胺转运体具有高亲和力和选择性相互作用的关键特征。然而，对三氟甲基取代基也是一个关键的结构要素。氟西汀的分子药理学已得到充分阐明，其体内药理作用似乎几乎完全由5-羟色胺摄取抑制介导。它对5-羟色胺转运体的选择性、对神经递质受体缺乏亲和力以及代谢为去甲氟西汀后仍保持选择性，使得氟西汀成为探索药理学诱导的5-羟色胺神经传递增加的有用工具。氟西汀已发现多种治疗用途。其在治疗抑郁症方面的应用研究最为广泛，但对照临床研究也表明该药物可能在治疗肥胖症和贪食症方面发挥作用。此外，该药物可能可用于治疗多种其他精神疾病。无论这些临床试验的结果如何，显然氟西汀已在治疗中找到了一个有用的定位，并且可作为一种探针来确定5-羟色胺在调节人类病理生理学中的作用。
