School of Pharmacy, Ningxia Medical University, 1160 Shengli St, Xingqing District, Yinchuan, Ningxia, China.
Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, 1160 Shengli St, Xingqing District, Yinchuan, Ningxia, China.
CNS Drugs. 2024 Dec;38(12):985-1002. doi: 10.1007/s40263-024-01123-x. Epub 2024 Oct 8.
Major depressive disorder (MDD) is a severe mental illness with a complex etiology. Currently, many medications employed in clinical treatment exhibit limitations such as delayed onset of action and a high incidence of adverse reactions. Therefore, there is a pressing need to develop antidepressants that exhibit enhanced efficacy and safety. The N-methyl-D-aspartate receptor (NMDAR), a distinctive glutamate-gated ion channel receptor, has been implicated in the onset and progression of depressive disorder, as evidenced by both preclinical and clinical research. The NMDAR antagonist, ketamine, exhibits rapid and sustained antidepressant effects, holding promise as a novel therapeutic approach for depressive disorder. However, its psychotomimetic impact and potential for addiction have restricted its widespread clinical application. Notably, over the past decade, studies have suggested that enhancing NMDAR functionality can produce antidepressant effects with improved safety, especially with the emergence of NMDAR-positive allosteric modulators (PAMs). We view this as a potential novel strategy for treating depression, forming the basis for the narrative review that follows.
重度抑郁症（MDD）是一种严重的精神疾病，其病因复杂。目前，许多用于临床治疗的药物在起效时间和不良反应发生率等方面存在局限性。因此，开发疗效更好、安全性更高的抗抑郁药物迫在眉睫。N-甲基-D-天冬氨酸受体（NMDAR）是一种独特的谷氨酸门控离子通道受体，其在抑郁症的发病和进展中的作用已被临床前和临床研究证实。NMDAR 拮抗剂氯胺酮具有快速和持续的抗抑郁作用，有望成为治疗抑郁症的一种新方法。然而，其致幻作用和成瘾潜力限制了其广泛的临床应用。值得注意的是，在过去十年中，研究表明增强 NMDAR 功能可以产生具有更好安全性的抗抑郁作用，尤其是出现 NMDAR 正变构调节剂（PAMs）后。我们认为这是一种治疗抑郁症的潜在新策略，这也是我们进行叙述性综述的基础。
