Mood disorders represent the largest cause of disability worldwide. The monoaminergic deficiency hypothesis, which has dominated the conceptual framework for researching the pathophysiology of mood disorders and the development of novel treatment strategies, cannot fully explain the underlying neurobiology of mood disorders. Mounting evidence collected over the past two decades suggests the amino acid neurotransmitter systems (glutamate and GABA) serve central roles in the pathophysiology of mood disorders. Here, we review progress in the development of compounds that act on these systems as well as their purported mechanisms of action. We include glutamate-targeting drugs, such as racemic ketamine, esketamine, lanicemine (AZD6765), traxoprodil (CP-101,606), EVT-101, rislenemdaz (CERC-301/MK-0657), AVP-786, AXS-05, rapastinel (formerly GLYX-13), apimostinel (NRX-1074/AGN-241660), AV-101, NRX-101, basimglurant (RO4917523), decoglurant (RG-1578/RO4995819), tulrampator (CX-1632/S-47445), and riluzole; and GABA-targeting agents, such as brexanolone (SAGE-547), ganaxolone, and SAGE-217.

中文翻译：

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新一代抗抑郁药：基于谷氨酸/GABA 神经递质系统的新型快速作用治疗情绪障碍的药物管道的更新。

情绪障碍是全世界残疾的最大原因。单胺能缺乏假说主导了情绪障碍病理生理学研究和新型治疗策略开发的概念框架，但无法完全解释情绪障碍的潜在神经生物学。过去二十年收集的越来越多的证据表明，氨基酸神经递质系统（谷氨酸和 GABA）在情绪障碍的病理生理学中发挥着核心作用。在这里，我们回顾了作用于这些系统的化合物的开发进展及其据称的作用机制。我们包括谷氨酸靶向药物，例如外消旋氯胺酮、艾氯胺酮、兰尼塞明 (AZD6765)、曲索普地尔 (CP-101,606)、EVT-101、rislenemdaz (CERC-301/MK-0657)、AVP-786、AXS-05、rapastinel （以前称为 GLYX-13）、apimostinel (NRX-1074/AGN-241660)、AV-101、NRX-101、basimglurant (RO4917523)、decoglurant (RG-1578/RO4995819)、tulrampator (CX-1632/S-47445)和利鲁唑；GABA 靶向药物，例如 brexanolone (SAGE-547)、ganaxolone 和 SAGE-217。