Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs
Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs
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DOI：
10.1016/j.bcp.2015.03.011
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发表时间：
2015-05-15
影响因子：
5.8
通讯作者：
Sanchez, Connie
中科院分区：
文献类型：
--
作者：
Dale, Elena;Bang-Andersen, Benny;Sanchez, Connie
在过去的几十年里，单胺假说一直是抑郁症的流行假说。它指出抑郁症与单胺功能降低有关。因此，自20世纪60年代以来，通过抑制5-羟色胺（5-HT）和去甲肾上腺素（NE）转运蛋白来增加单胺传递的努力一直是抑郁症研究的中心主题。选择性5-HT再摄取抑制剂（SSR 1）和5-HT和NE再摄取抑制剂（SNRIs）已出现从这条线的研究是目前的一线治疗选择的抑郁症（MOD）。抗抑郁药研究的最新趋势之一是通过靶向单胺能受体和其他转运蛋白（例如，使用多模式药物和三重再吸收抑制剂）或通过在SSR 1或SNRI治疗中添加非典型抗精神病药物来完善单胺能机制。此外，在临床前和临床研究中，基于疾病的生物学特征和药物干预的疗效，提出了抑郁症的其他几种假设。一个核心策略是靶向谷氨酸受体（例如，静脉输注N-甲基-c-天冬氨酸（NMDA）受体拮抗剂氯胺酮）。其他策略基于胆碱能和γ-氨基丁酸（GABA）能传递、神经元可塑性、应激/下丘脑垂体肾上腺（HPA）轴、奖赏系统和神经炎症的调节。在这里，我们回顾了来自这些策略的化合物的药理学概况，并在最近的临床试验中进行了测试，并发表了结果。此外，我们还讨论了正在临床前水平研究的抑郁症的假定治疗方法，并概述了抗抑郁药研究的未来方向。(C)2015年，作者。爱思唯尔公司出版
The monoamine hypothesis has been the prevailing hypothesis of depression over the last several decades. It states that depression is associated with reduced monoamine function. Hence efforts to increase monoamine transmission by inhibiting serotonin (5-HT) and norepinephrine (NE) transporters has been a central theme in depression research since the 1960s. The selective 5-HT reuptake inhibitors (SSR1s) and 5-HT and NE reuptake inhibitors (SNRIs) that have emerged from this line of research are currently first line treatment options for major depressive disorder (MOD). One of the recent trends in antidepressant research has been to refine monoaminergic mechanisms by targeting monoaminergic receptors and additional transporters (e.g. with multimodal drugs and triple re-uptake inhibitors) or by adding atypical antipsychotics to SSR1 or SNRI treatment. In addition, several other hypotheses of depression have been brought forward in pre-clinical and clinical research based on biological hallmarks of the disease and efficacy of pharmacological interventions. A central strategy has been to target glutamate receptors (for example, with intravenous infusions of the N-methyl-c-aspartate (NMDA) receptor antagonist ketamine). Other strategies have been based on modulation of cholinergic and gamma-aminobutyric acid (GABA)ergic transmission, neuronal plasticity, stress/hypothalamic pituitary adrenal(HPA)-axis, the reward system and neuroinflammation. Here we review the pharmacological profiles of compounds that derived from these strategies and have been recently tested in clinical trials with published results. In addition, we discuss putative treatments for depression that are being investigated at the preclinical level and outline future directions for antidepressant research. (C) 2015 The Authors. Published by Elsevier Inc.