脑内组胺H_(3)受体反向激动剂必妥利生:促醒及治疗睡眠和认知障碍新疗法  

Histamine H_(3)-receptor inverse agonist pitolisant,a novel therapy to improve wakefulness and to normalize sleep and cognitive disorders

作　　者：赵妍 王治 林建生 缪朝玉 ZHAO Yan;WANG Zhi;LIN Jian-sheng;MIAO Chao-yu(Dept of Pharmacology,Naval Medical University/Second Military Medical University,Shanghai 200433,China;Intergrative Physiology of the Brain Arousal System,Claude Bernard University,Lyon 69675,France)

机构地区：[1]海军军医大学药学系药理学教研室,上海200433 [2]法国国家健康与医学研究院,里昂大学大脑清醒机制研究室,里昂69675

出　　处：《中国药理学通报》2022年第11期1622-1626,共5页Chinese Pharmacological Bulletin

基　　金：上海市卫生健康委员会卫生行业临床研究专项(No.202140011);上海市科委“科技创新行动计划”(No.21140901000)。

摘　　要：必妥利生(pitolisant)是由法国Bioprojet集团合成的口服小分子组胺H_(3)受体反向激动剂,经里昂大学INSERM清醒机制研究室在正常和病理动物模型中发现其促醒效应后并经临床检验,先后于2016和2019年由欧盟医药委员会和美国食品药品管理局批准用于治疗发作性睡病白天过度嗜睡(excessive daytime sleepiness,EDS)和猝倒。该文介绍和综述本疗法的作用机制和靶点、临床特征及最新研究成果,期望未来该新药在我国临床精准应用,并探索开发新的适应症。Pitolisant is an orally active histamine H_(3)-receptor inverse agonist developed by Bioprojet.Following identification of its wake/cognitive-improving effects in normal animals and in a murine narcoleptic model and then after preclinical and clinical trials,Pitolisant was approved by European Medicines Agency(2016)and US FDA(2019)as the first choice for anti-narcoleptic therapy.Currently,the clinical indications for Pitolisant are being extended to other sleep disorders.The present short review summarized the mechanisms of action of Pitolisant and its brain targets,clinical use and the latest research findings.We hope to introduce this novel therapy to Chinese readers in order to promote its precision use in sleep medicine in China and exploration of new potential clinical indications.

关 键 词：必妥利生 促醒药物 组胺H_(3)受体 睡眠障碍 白天过度嗜睡 认知障碍 

分 类 号：R338.63[医药卫生—人体生理学] R392.11[医药卫生—基础医学] R395.2[哲学宗教—心理学] R741[医药卫生—医学心理学] R971