氯胺酮快速抗抑郁机制及不良反应的研究进展  

Research progress of rapid antidepressant mechanism and side effects of ketamine

作　　者：齐士魁 高静 马科文 聂晨晨 冯晓东[1,2] QI Shikui;GAO Jing;MA Kewen;NIE Chenchen;FENG Xiaodong(Henan University of Chinese Medicine,Zhengzhou 450000,China;The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China)

机构地区：[1]河南中医药大学,河南郑州450000 [2]河南中医药大学第一附属医院,河南郑州450000

出　　处：《沈阳药科大学学报》2024年第1期128-139,共12页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金青年基金资助项目(82104973)。

摘　　要：目的对氯胺酮治疗抑郁症的可能作用机制及临床不良反应进行系统阐述,以期为氯胺酮的临床研究及新一代抗抑郁药的研制提供思路及参考。方法从中国知网(CNKI)、万方中文数据库、Web of Science数据库及PubMed数据库检索2012年5月至2022年5月收录的相关文献;以“氯胺酮、艾司氯胺酮、抑郁症、难治性抑郁症、重度抑郁症、N-甲基-D-天冬氨酸受体、α-氨基-3-羟基-5-甲基-4-异恶唑-丙酸受体、脑源性神经营养因子、雷帕霉素靶蛋白、肠道菌群、真核延伸因子2激酶、不良反应”为中文检索词,以“ketamine,esketamine,depression,treatment resistant depression,major depressive disorder,NMDAR,AMPAR,BDNF,TOR,gut microbiota,eEF2K,side effect”为英文检索词,最终纳入83篇文献进行研究分析。结果与结论氯胺酮是一种N-甲基-D-天冬氨酸受体(N-methyl-d-aspartate receptors,NMDAR)拮抗剂,由(S)-氯胺酮和(R)-氯胺酮两种对映异构体按照1∶1的比例构成。已有证据表明其对抑郁症的治疗有着显著疗效。研究显示,氯胺酮的作用机制可能与NMDAR、α-氨基-3-羟基-5-甲基-4-异恶唑-丙酸受体(α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor,AMPAR)、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)、肠道菌群、真核延伸因子2激酶(eukaryotic elongation factor 2 kinase,eEF2K)等有关。同时,多项研究显示氯胺酮可能导致神经毒性反应、拟精神病、心血管系统疾病,以及泌尿系统疾病等多种不良反应,导致其在临床应用及试验中存在一定局限性。因此,深入探讨氯胺酮的作用机制及临床不良反应应,探索氯胺酮可能的作用靶点极其重要。Objective To systematically describe the possible mechanism of action and clinical side effects of ketamine in the treatment of depression,in order to provide ideas and reference for the clinical research of ketamine and the development of a new generation of antidepressants.Methods Relevant literatures were retrieved from CNKI,Wanfang Chinese Database,Web of Science database and PubMed database until May 2022.“Ketamine,esketamine,depression,treatment-resistant depression(TRD),major depressive disorder(MMD),N-methyl-D-aspartate receptors(NMDAR),α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor(AMPAR),brain derived neurotrophic factor(BDNF),mammalian target of rapamycin(mTOR),gut microbiota,eukaryotic extended factor of 2 kinase(eEFK2)and side effect”for the word retrieval.Finally,83 literatures were included for research and analysis.Results&Conclusions Ketamine is a N-methyl-D-Aspartate receptor(NMDAR)antagonist,consisting of(S)-ketamine and(R)-ketamine enantiomers in a 1:1 ratio.It has turned out to be effective in the treatment of depression.Research demonstrated that the mechanism of ketamine may be related to NMDAR,AMPAR,BDNF,mTOR,gut microbiota and eEF2K.More importantly,a number of studies have shown that ketamine may cause neurotoxic reactions,psychosis,cardiovascular system diseases,urinary system diseases and other side effects,thus leading to some limitations in its clinical application and testing.Therefore,it is extremely important to explore the mechanism and clinical side effects of ketamine and the possible targets of ketamine.

关 键 词：氯胺酮 抑郁症 N-甲基-D-天冬氨酸受体 α-氨基-3-羟基-5-甲基-4-异恶唑-丙酸受体 不良反应 

分 类 号：R96[医药卫生—药理学]