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

作　　者：Kai Yuan Ying Han Kenji Hashimoto Lin Lu 

机构地区：[1]Institute of Mental Health,National Clinical Research Center for Mental Disorders,Key Laboratory of Mental Health and Peking University Sixth Hospital,Peking University [2]Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research,Peking University [3]National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence,Peking University [4]Division of Clinical Neuroscience,Chiba University Center for Forensic Mental Health

出　　处：《Neuroscience Bulletin》2016年第6期565-568,共4页神经科学通报（英文版）

摘　　要：Ketamine is a noncompetitive N-methyl-D-aspartate receptor （NMDAR） antagonist that has attracted wide- spread attention for its rapid-onset antidepressant effects, especially in individuals with treatment-resistant depres- sion and suicidal ideation [1-3]. Compared with the tra- ditional 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 [1, 2, 4]. However, ketamine still has limited clinical application, psychotomimetic side-effects and liability of abuse. A recent paper in Nature [5] 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 land- mark in the field of depression. Investigations of its mechanism of action will inspire the development of a newKetamine is a noncompetitive N-methyl-D-aspartate receptor （NMDAR） antagonist that has attracted wide- spread attention for its rapid-onset antidepressant effects, especially in individuals with treatment-resistant depres- sion and suicidal ideation [1-3]. Compared with the tra- ditional 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 [1, 2, 4]. However, ketamine still has limited clinical application, psychotomimetic side-effects and liability of abuse. A recent paper in Nature [5] 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 land- mark in the field of depression. Investigations of its mechanism of action will inspire the development of a new

关 键 词：NMDAR Ketamine and Its Metabolites On the Eve of Upgrading Antidepressants 

分 类 号：R749.4[医药卫生—神经病学与精神病学]