The robust antidepressant effects of (R,S)-ketamine are among the most important discoveries in mood research over the last half century. Off-label use of (R,S)-ketamine, which is an equal mixture of (R)-ketamine and (S)-ketamine, has become especially popular in the United States (US) for treatment-resistant depression. On March 5, 2019, the US Food and Drug Administration approved an (S)-ketamine nasal spray for use in treatment-resistant depression, though its use has been limited to certified medical offices or clinics. On December 19, 2019, (S)-ketamine nasal spray was approved for the same indication in Europe. However, despite its potential for benefit, there are several concerns about the efficacy of (S)-ketamine nasal spray. Accumulating evidence from preclinical studies show that (R)-ketamine has greater potency and longer lasting antidepressant effects than (S)-ketamine in animal models of depression, and that (R)-ketamine has fewer detrimental side effects than either (R,S)-ketamine or (S)-ketamine. As such, clinical studies of (R)-ketamine in humans are now underway by Perception Neuroscience Ltd. In this article, we review the brief history of (R,S)-ketamine and its two enantiomers as novel antidepressants. We also discuss the mechanisms of ketamine's antidepressant actions.

（R，S）-氯胺酮的强大抗抑郁作用是过去半个世纪情绪研究中最重要的发现之一。（R，S）-氯胺酮的标签外使用是（R）-氯胺酮和（S）-氯胺酮的均等混合物，在美国（US）中对于抗药性抑郁症尤其流行。2019年3月5日，美国食品和药物管理局批准了一种（S）-氯胺酮鼻喷雾剂，可用于抗药性抑郁症，尽管其使用仅限于经过认证的医疗机构或诊所。在2019年12月19日，（S氯胺酮鼻喷雾剂在欧洲被批准用于相同的适应症。然而，尽管其具有潜在的益处，但是对于（S）-氯胺酮鼻喷雾剂的功效存在一些担忧。从临床前研究越来越多的证据表明，（[R ）氯胺酮具有更大的效力更持久比（抗抑郁作用小号在抑郁症动物模型）氯胺酮，以及（[R ）氯胺酮有有害的副作用比任何（少[R ，小号）-氯胺酮或（S）-氯胺酮。因此，Perception Neuroscience Ltd.目前正在进行人体中（R）-氯胺酮的临床研究。在本文中，我们回顾了（R，S）-氯胺酮及其两种对映体为新型抗抑郁药。我们还讨论了氯胺酮抗抑郁作用的机制。