Owens M J, Knight D L, Nemeroff C B
Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA.
Biol Psychiatry. 2001 Sep 1;50(5):345-50. doi: 10.1016/s0006-3223(01)01145-3.
Single isomers of the selective serotonin reuptake inhibitors citalopram (escitalopram, S-citalopram) and fluoxetine (R-fluoxetine) are currently under development for the treatment of depression and other psychiatric disorders. Previous studies conducted in laboratory animals have revealed that the biological effects on serotonin reuptake for citalopram reside in the S enantiomer. In contrast, both enantiomers of fluoxetine contribute to its biological activity.
In the present study, the potency and selectivity of escitalopram, R-fluoxetine, and all of the other currently available selective serotonin reuptake inhibitors were compared for binding affinity at the human serotonin, norepinephrine, and dopamine transporters and several select neurotransmitter receptors using radioligand binding assays.
Both escitalopram and R-fluoxetine were potent inhibitors of the serotonin transporter (K(i) = 1.1 and 1.4 nmol/L, respectively). Escitalopram was the most serotonin transporter-selective compound tested and was approximately 30-fold more potent than R-citalopram.
As noted previously, paroxetine and sertraline possess moderate affinity (<50 nmol/L) for the human norepinephrine transporter and dopamine transporter, respectively. R-Fluoxetine, unlike the other selective serotonin reuptake inhibitors, possesses moderate affinity (K(i) = 64 nmol/L) for the serotonin 2C receptor. Potential clinical correlates of these unique attributes of escitalopram and R-fluoxetine are discussed.
选择性5-羟色胺再摄取抑制剂西酞普兰（艾司西酞普兰，S-西酞普兰）和氟西汀（R-氟西汀）的单一异构体目前正在开发用于治疗抑郁症和其他精神疾病。先前在实验动物中进行的研究表明，西酞普兰对5-羟色胺再摄取的生物学效应存在于S对映体中。相比之下，氟西汀的两种对映体均对其生物学活性有贡献。
在本研究中，使用放射性配体结合试验，比较了艾司西酞普兰、R-氟西汀以及所有其他目前可用的选择性5-羟色胺再摄取抑制剂对人5-羟色胺、去甲肾上腺素和多巴胺转运体以及几种选定神经递质受体的结合亲和力的效力和选择性。
艾司西酞普兰和R-氟西汀均为5-羟色胺转运体的强效抑制剂（抑制常数分别为1.1和1.4 nmol/L）。艾司西酞普兰是所测试的最具5-羟色胺转运体选择性的化合物，其效力比R-西酞普兰高约30倍。
如先前所述，帕罗西汀和舍曲林分别对人去甲肾上腺素转运体和多巴胺转运体具有中等亲和力（<50 nmol/L）。与其他选择性5-羟色胺再摄取抑制剂不同，R-氟西汀对5-羟色胺2C受体具有中等亲和力（抑制常数 = 64 nmol/L）。讨论了艾司西酞普兰和R-氟西汀这些独特特性的潜在临床相关性。
