Research progress on the mechanism of rapid antidepressant action of hydronorketamine

中华行为医学与脑科学杂志 Pub Date : 2020-02-20 DOI:10.3760/CMA.J.CN371468-20190605-00364

Xianqiang Zhang, Bo Lian, Changjiang Li, Guohua Lu, Hongwei Sun, Lin Sun

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引用次数: 0

Abstract

Major depressive disorder is a mental illness characterized by depressed mood, lack of engagement in pleasurable activities, anhedonia, and cognitive-behavioral disorders. Currently, traditional pharmacological treatments for depression have a delayed therapeutic onset and low treatment effectiveness. (2R, 6R)-HNK, as a key metabolite of ketamine, can not only exert rapid and lasting antidepressant effects but also has no side effects such as hallucination and addiction caused by ketamine, which has potential clinical application values. Studies have found that the antidepressant effect of (2R, 6R)-HNK is closely related to the regulation mechanism of glutamate receptor and synaptic plasticity. Besides, the changes of downstream signaling pathways include the upregulation of brain-derived neurotrophic factor (BDNF) expression, dephosphorylation of eukaryotic elongation factor 2 (eEF2), and activation of the mammalian target of rapamycin (mTOR) play a key role in the antidepressant process of the drug. Understanding the molecular mechanisms underpinning (2R, 6R)-HNK's antidepressant effects will be invaluable for the identification of targets, which will drive the development of novel, effective, next-generation pharmacotherapies for the treatment of depression. Key words: Depression; (2R, 6R)-hydronorketamine; Glutamate; Antidepressant

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氢羟氯胺酮快速抗抑郁作用机制的研究进展

重度抑郁症是一种精神疾病，其特征是情绪低落、缺乏愉快活动、快感缺乏和认知行为障碍。目前，传统的抑郁症药物治疗具有治疗延迟和治疗效果低的特点。（2R，6R）-HNK作为氯胺酮的关键代谢产物，不仅能发挥快速持久的抗抑郁作用，而且没有氯胺酮引起的幻觉、成瘾等副作用，具有潜在的临床应用价值。研究发现，（2R，6R）-HNK的抗抑郁作用与谷氨酸受体的调节机制和突触可塑性密切相关。此外，下游信号通路的变化包括脑源性神经营养因子（BDNF）表达的上调、真核延伸因子2（eEF2）的去磷酸化和哺乳动物雷帕霉素靶点（mTOR）的激活在药物的抗抑郁过程中起着关键作用。了解（2R，6R）-HNK抗抑郁作用的分子机制对于确定靶点将是非常宝贵的，这将推动开发新的、有效的、下一代治疗抑郁症的药物疗法。关键词：抑郁症；（2R，6R）-水合Worketamine；谷氨酸；抗抑郁药

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来源期刊

中华行为医学与脑科学杂志

自引率

0.00%

发文量

8131

期刊介绍： "Chinese Journal of Behavioral Medicine and Brain Science" (CN 37-1468/R, ISSN 1674-6554) is a national academic journal under the supervision of the National Health Commission, sponsored by the Chinese Medical Association and Jining Medical College. The journal was founded in June 1992 and was formerly known as "Chinese Journal of Behavioral Medicine" (1992-1993) and "Chinese Behavioral Medical Science" (1994-2008). In 2009, it was renamed "Chinese Journal of Behavioral Medicine and Brain Science" with the approval of the State Administration of Press, Publication, Radio, Film and Television. The purpose of "Chinese Journal of Behavioral Medicine and Brain Science" is to implement the health and health policies of the Party and the State, implement the principle of combining theory with practice and popularization and improvement, and reflect the major progress in the theory and practical application of behavioral medicine and brain science in my country. It publishes academic papers and scientific research results in the field of behavioral medicine and brain science in my country, and has columns such as monographs/reviews, basic research, clinical research, health prevention, methods and techniques, psychological behavior and evaluation, and systematic evaluation.