On the Eve of Upgrading Antidepressants: (R)-Ketamine and Its Metabolites

Ketamine is a noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist that has attracted widespread attention for its rapid-onset antidepressant effects, especially in individuals with treatment-resistant depression and suicidal ideation. Compared with the traditional antidepressants that take weeks, if not months, to benefit patients and are associated with a high rate of relapse, ketamine exerts its antidepressant effects within several hours. These clinical benefits can last for 2 weeks after a single injection. However, ketamine still has limited clinical application, mainly because of its psychotomimetic side-effects and liability of abuse. A recent paper in Nature showed that the ketamine metabolite enantiomer (2R,6R)-hydroxynorketamine (HNK) has rapid and sustained antidepressant effects without the side-effects associated with ketamine, such as abuse potential. The discovery of (R)-ketamine is a landmark in the field of depression. Investigations of its mechanism of action will inspire the development of a new generation of rapid-acting antidepressants that are safer and have few dissociative side-effects.SCI(E)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)EDITORIAL MATERIALlinlu@bjmu.edu.cn6565-5683