中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (4): 727-733.doi: 10.4103/1673-5374.353479

• 综述:退行性病与再生 • 上一篇    下一篇

治疗神经退行性疾病记忆障碍的新型药物：阿戈美拉汀

  

  • 出版日期:2023-04-15 发布日期:2022-10-27
  • 基金资助:
    山西省“1331工程”重点学科建设项目（1331KSC）；山西省博士科研启动基金项目（SD2011）；山西医科大学博士科研启动基金项目（XD2017）

Agomelatine: a potential novel approach for the treatment of memory disorder in neurodegenerative disease

Qiang Su1, 2, 3, #, Tian Li1, 2, #, Guo-Wei Liu4, Yan-Li Zhang3, 5, Jun-Hong Guo3, *, Zhao-Jun Wang1, 2, Mei-Na Wu1, 2, Jin-Shun Qi1, 2, *   

  1. 1Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi Province, China;  2Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi Province, China;  3Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China;  4Department of Laboratory Medicine, Fenyang College of Shanxi Medical University, Fenyang, Shanxi Province, China; 5Department of Neurology, Sixth Hospital of Shanxi Medical University (General Hospital of Tisco), Taiyuan, Shanxi Province, China
  • Online:2023-04-15 Published:2022-10-27
  • Contact: Jin-Shun Qi, PhD, jinshunqi2009@163.com.
  • Supported by:
    The work was supported by Shanxi “1331 Project” Key Subjects Construction, No. 1331KSC (to JSQ); Science Research Start-up Fund for Doctors of Shanxi Province, No. SD2011 (to TL); and Science Research Start-Up Fund for Doctors of Shanxi Medical University, No. XD2017 (to TL).

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摘要：

阿戈美拉汀是一种选择性褪黑素受体MT1/MT2激动剂和血清素5-羟色胺2C受体拮抗剂，已在临床上用于治疗成人重度抑郁。阿戈美拉汀能通过激动褪黑素受体MT1/MT2，重建睡眠-觉醒节律，以使昼夜节律正常化，同时发挥抗抑郁和抗焦虑作用。阿戈美拉汀还可通过拮抗新皮质突触后5-羟色胺2C受体，调控前额皮质中多巴胺和去甲肾上腺素的分泌，增加多巴胺和去甲肾上腺素的活性，进而改善抑郁、焦虑等情绪异常表现。这两种作用的有效结合使得阿戈美拉汀在对抗抑郁、焦虑及睡眠节律紊乱治疗中显示出特有的药理作用。情绪和睡眠与记忆、认知功能密切相关，而记忆和认知损害是多数神经退行性疾病、精神疾病的常见临床症状。因此阿戈美拉汀能否在治疗抑郁和睡眠节律紊乱的同时改善患者的学习记忆以及认知活动引起了人们的兴趣和关注。此次综述回顾性总结了临床试验和动物实验中阿戈美拉汀治疗精神和睡眠节律障碍影响的最新发现，以期为精神疾病和神经退行性疾病的记忆和认知障碍治疗提出可借鉴的策略。

https://orcid.org/0000-0001-9223-8806 (Jin-Shun Qi)

关键词: 阿戈美拉汀, 褪黑素, 抗抑郁药, 情绪障碍, 抑郁, 焦虑, 冷漠, 睡眠节律障碍, 记忆障碍, 认知功能障碍, 神经退行性疾病

Abstract: Agomelatine is a selective agonist of melatonin receptor 1A/melatonin receptor 1B (MT1/MT2) and antagonist of 5-hydroxytryptamine 2C receptors. It is used clinically to treat major depressive episodes in adults. The pro-chronobiological activity of agomelatine reconstructs sleep-wake rhythms and normalizes circadian disturbances via its agonistic effect of melatonin receptor 1A/melatonin receptor 1B, which work simultaneously to counteract depression and anxiety disorder. Moreover, by antagonizing neocortical postsynaptic 5-hydroxytryptamine 2C receptors, agomelatine enhances the release of dopamine and noradrenaline in the prefrontal cortex, increases the activity of dopamine and noradrenaline, and thereby reduces depression and anxiety disorder. The combination of these two effects means that agomelatine exhibits a unique pharmacological role in the treatment of depression, anxiety, and disturbance of the circadian rhythm. Emotion and sleep are closely related to memory and cognitive function. Memory disorder is defined as any forms of memory abnormality, which is typically evident in a broad range of neurodegenerative diseases, including Alzheimer’s disease. Memory impairment and cognitive impairment are common symptoms of neurodegenerative and psychiatric diseases. Therefore, whether agomelatine can improve memory and cognitive behaviors if used for alleviating depression and circadian-rhythm sleep disorders has become a research “hotspot”. This review presents the latest findings on the effects of agomelatine in the treatment of psychologic and circadian-rhythm sleep disorders in clinical trials and animal experiments. Our review evaluates recent studies on treatment of memory impairment and cognitive impairment in neurodegenerative and psychiatric diseases.

Key words: agomelatine, antidepressant, anxiety, apathy, circadian-rhythm sleep disorder, cognitive impairment, depression, melatonergic, memory disorder, mood disorder, neurodegenerative disease