David D J, Tritschler L, Guilloux J-P, Gardier A M, Sanchez C, Gaillard R
Inserm UMR-S 1178 Santé Mentale et Santé Publique, Université Paris-Sud, Fac Pharmacie, Université Paris Saclay, Châtenay-Malabry, France; DJD et LT ont contribué de façon équivalente à l'élaboration du manuscrit.
Inserm UMR-S 1178 Santé Mentale et Santé Publique, Université Paris-Sud, Fac Pharmacie, Université Paris Saclay, Châtenay-Malabry, France.
Encephale. 2016 Feb;42(1 Suppl 1):1S12-23. doi: 10.1016/S0013-7006(16)30015-X.
Selective Serotonin Reuptake Inhibitors (SSRIs) are extensively used for the treatment of major depressive disorder (MDD). SSRIs are defined as indirect receptor agonists since the activation of postsynaptic receptors is a consequence of an increase in extracellular concentrations of serotonin (5-HT) mediated by the blockade of serotonin transporter. The activation of some serotoninergic receptors (5-HT1A, post-synaptic, 5-HT1B post-synaptic, 5-HT2B, and 5-HT4), but not all (5-HT1A, pre-synaptic, 5-HT1B pre-synaptic, 5-HT2A, 5-HT2C, 5-HT3, and probably 5-HT6), induces anxiolytic/antidepressive - like effects. Targetting specifically some of them could potentially improve the onset of action and/or efficacy and/or prevent MD relapse. Vortioxetine (Brintellix, 1- [2-(2,4-dimethylphenyl-sulfanyl)-phenyl]-piperazine) is a novel multi-target antidepressant drug approved by the Food and Drug Administration (FDA) and by European Medicines Agency. Its properties are markedly different from the extensively prescribed SSRIs. Compared to the SSRIs, vortioxetine is defined as a multimodal antidepressant drug since it is not only a serotonin reuptake inhibitor, but also a 5-HT1D, 5-HT3, 5-HT7 receptor antagonist, 5-HT1B receptor partial agonist and 5-HT1A receptor agonist. This specific pharmacological profile enables vortioxetine to affect not only the serotoninergic and noradrenergic systems, but also the histaminergic, cholinergic, gamma-butyric acid (GABA) ergic and glutamatergic ones. Thus, vortioxetine not only induces antidepressant-like or anxiolytic-like activity but also improves cognitive parameters in several animal models. Indeed, vortioxetine was shown to improve working memory, episodic memory, cognitive flexibility and spatial memory in young adult rodents and also in old animal models. These specific effects of the vortioxetine are of interest considering that cognitive dysfunction is a common comorbidity to MDD. Altogether, even though this molecule still needs to be investigated further, especially in the insufficient-response to antidepressant drugs, vortioxetine is already an innovative therapeutic option for the treatment of major depression.
选择性5-羟色胺再摄取抑制剂（SSRIs）被广泛用于治疗重度抑郁症（MDD）。SSRIs被定义为间接受体激动剂，因为突触后受体的激活是由5-羟色胺转运体的阻断介导的细胞外5-羟色胺（5-HT）浓度增加的结果。一些5-羟色胺能受体（5-HT1A，突触后；5-HT1B，突触后；5-HT2B和5-HT4）的激活会诱导抗焦虑/抗抑郁样效应，但并非所有受体（5-HT1A，突触前；5-HT1B，突触前；5-HT2A、5-HT2C、5-HT3以及可能的5-HT6）都会如此。特异性靶向其中一些受体可能会潜在地改善起效时间和/或疗效和/或预防MDD复发。伏硫西汀（心达悦，Brintellix，1-[2-(2,4-二甲基苯基硫烷基)-苯基]-哌嗪）是一种经美国食品药品监督管理局（FDA）和欧洲药品管理局批准的新型多靶点抗抑郁药。其特性与广泛使用的SSRIs明显不同。与SSRIs相比，伏硫西汀被定义为一种多模式抗抑郁药，因为它不仅是一种5-羟色胺再摄取抑制剂，还是一种5-HT1D、5-HT3、5-HT7受体拮抗剂、5-HT1B受体部分激动剂和5-HT1A受体激动剂。这种特定的药理学特征使伏硫西汀不仅能影响5-羟色胺能和去甲肾上腺素能系统，还能影响组胺能、胆碱能、γ-氨基丁酸（GABA）能和谷氨酸能系统。因此，伏硫西汀不仅能诱导抗抑郁样或抗焦虑样活性，还能在多种动物模型中改善认知参数。事实上，在年轻成年啮齿动物和老年动物模型中，伏硫西汀都被证明能改善工作记忆能力（working memory）、情景记忆、认知灵活性和空间记忆。考虑到认知功能障碍是MDD常见的共病，伏硫西汀的这些特定作用值得关注。总之，尽管这种分子仍需进一步研究，特别是在对抗抑郁药反应不足的情况下，但伏硫西汀已经是治疗重度抑郁症的一种创新治疗选择。
