Goodnick P J, Goldstein B J
Department of Psychiatry and Behavioral Sciences, Health Services Research Center, University of Miami School of Medicine, Florida 33136, USA.
J Psychopharmacol. 1998;12(3 Suppl B):S5-20. doi: 10.1177/0269881198012003021.
The selective serotonin reuptake inhibitors (SSRIs), citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, are the result of rational research to find drugs that were as effective as the tricyclic antidepressants but with fewer safety and tolerability problems. The SSRIs selectively and powerfully inhibit serotonin reuptake and result in a potentiation of serotonergic neurotransmission. The property of potent serotonin reuptake appears to give a broad spectrum of therapeutic activity in depression, anxiety, obsessional and impulse control disorders. However, despite the sharing of the same principal mechanism of action, SSRIs are structurally diverse with clear variations in their pharmacodynamic and pharmacokinetic profiles. The potency for serotonin reuptake inhibition varies amongst this group, as does the selectivity for serotonin relative to noradrenaline and dopamine reuptake inhibition. The relative potency of sertraline for dopamine reuptake inhibition differentiates it pharmacologically from other SSRIs. Affinity for neuroreceptors, such as sigma1, muscarinic and 5-HT2c, also differs widely. Furthermore, the inhibition of nitric oxide synthetase by paroxetine, and possibly other SSRIs, may have significant pharmacodynamic effects. Citalopram and fluoxetine are racemic mixtures of different chiral forms that possess varying pharmacokinetic and pharmacological profiles. Fluoxetine has a long acting and pharmacologically active metabolite. There are important clinical differences among the SSRIs in their pharmacokinetic characteristics. These include differences in their half-lives, linear versus non-linear pharmacokinetics, effect of age on their clearance and their potential to inhibit drug metabolising cytochrome P450 (CYP) isoenzymes. These pharmacological and pharmacokinetic differences underly the increasingly apparent important clinical differences amongst the SSRIs.
选择性5-羟色胺再摄取抑制剂（SSRI），如西酞普兰、氟西汀、氟伏沙明、帕罗西汀和舍曲林，是合理研究的成果，旨在找到与三环类抗抑郁药效果相当，但安全性和耐受性问题较少的药物。SSRI选择性且强效地抑制5-羟色胺再摄取，从而增强5-羟色胺能神经传递。强效的5-羟色胺再摄取特性似乎能在抑郁症、焦虑症、强迫症和冲动控制障碍中产生广泛的治疗活性。然而，尽管它们具有相同的主要作用机制，但SSRI在结构上各不相同，其药效学和药代动力学特征也有明显差异。该类药物中5-羟色胺再摄取抑制的效力各不相同，对5-羟色胺相对于去甲肾上腺素和多巴胺再摄取抑制的选择性也有所不同。舍曲林对多巴胺再摄取抑制的相对效力使其在药理学上与其他SSRI有所区别。对神经受体，如σ1、毒蕈碱和5-HT2c的亲和力也有很大差异。此外，帕罗西汀以及可能其他的SSRI对一氧化氮合酶的抑制作用可能具有显著的药效学效应。西酞普兰和氟西汀是具有不同药代动力学和药理学特征的不同手性形式的外消旋混合物。氟西汀有一个长效且具有药理活性的代谢物。SSRI在药代动力学特征方面存在重要的临床差异。这些差异包括它们的半衰期、线性与非线性药代动力学、年龄对其清除率的影响以及它们抑制药物代谢细胞色素P450（CYP）同工酶的潜力。这些药理学和药代动力学差异是SSRI之间日益明显的重要临床差异的基础。
