氯胺酮是一种离子型谷氨酸能N‑甲基‑D‑天冬氨酸受体（glutamatergic N‑methyl‑D‑aspartate receptor, NMDAR）拮抗剂，具有快速且持久的抗抑郁治疗作用，尤其对难治型抑郁症（treatment‑resistant depression, TRD）可有效改善临床症状。文章对氯胺酮抗抑郁作用的机制和分子基础进行综述，介绍NMDAR及α‑氨基‑3‑羟基‑5‑甲基‑4‑异恶唑丙酸受体（alpha‑amino‑3‑hydroxy‑5‑methyl‑4‑isoxazole propionic acid receptor, AMPAR）在氯胺酮及对映体药物治疗中的作用，探讨氯胺酮通过脑源性神经营养因子（brain‑derived neurotrophic factor, BDNF）、雷帕霉素靶蛋白（mammalian target of rapamycin, mTOR）及阿片受体介导发挥抗抑郁作用的机制，并对其他可能分子机制进行总结，以期为开发安全、有效的抗抑郁药物提供新的研究方向。
Ketamine is an antagonist of glutamatergic N‑methyl‑D‑aspartate receptor (NMDAR), with rapid and long‑lasting therapeutic effects on depression, and can effectively improve clinical symptoms of severe patients with treatment‑resistant depression(TRD). This paper reviews the mechanisms and molecular basis of ketamine's potent antidepressant effects, introduces the role of NMDAR and alpha‑amino‑3‑hydroxy‑5‑methyl‑4‑isoxazole propionic acid receptor (AMPAR) in the treatment with ketamine and its enantiomer. Meanwhile, this paper discusses how ketamine works as an antidepressant via brain‑derived neurotrophic factor (BDNF), mammalian target of rapamycin (mTOR) and opioid system, and summarizes other possible molecular mechanisms, so as to provide a new research direction for the development of safe and effective antidepressants.
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