中国临床药理学与治疗学2025，Vol.30Issue(12)：1615-1624,10.DOI:10.12092/j.issn.1009-2501.2025.12.004
促觉醒药物治疗发作性睡病研究进展
Research advances in wake-promoting drugs for the treatment of narcolepsy
摘要
Abstract
Narcolepsy(NT)is a rare central disor-der of hypersomnolence,categorized as type 1 or type 2 depending on whether there is loss of hypo-thalamic orexinergic neurons.Its core clinical fea-tures—excessive daytime sleepiness(EDS)and ab-normalities in REM sleep—significantly interfere with patients'educational attainment,work produc-tivity,and activities of daily living.Currently,wake-promoting agents(WPAs)remain the cornerstone of EDS symptom management.This article provides a systematic review of advances over the past de-cade in the treatment of NT-related EDS with WPAs.Traditional central nervous system stimulants—amphetamine,methyphenidate,modafinil and armodafinil—have the longest history of use,yet re-search progress on their pharmacological mecha-nisms and therapeutic optimization has been limit-ed in recent years.Novel WPAs,such as the dopa-mine and norepinephrine reuptake inhibitor solri-amfetol and the histamine H3 receptor antagonist/inverse agonist pitolisant,significantly improve both subjective and objective assessment indices of NT-related EDS by modulating monoaminergic and histaminergic wake-promoting pathways.The gam-ma-hydroxybutyrate(GHB)prodrug sodium oxy-bate,which consolidates nocturnal sleep and regu-lates cataplexy by activating gama-aminobutyric ac-id_B(GABA_B)receptors and modulating noradren-ergic and dopaminergic neuronal activity,has dem-onstrated equivalent efficacy to conventional for-mulations while reducing dosing frequency and car-diometabolic burden through its controlled-release and low-sodium formulations.Network meta-analy-ses indicate that the aforementioned WPAs exhibit favorable therapeutic efficacy in narcolepsy,and all three are recommended as first-line agents for NT-related EDS by domestic and international guideline consensus.Notably,orexin type 2 receptor agonists—the first etiology-targeted therapy—have com-pleted Phase III clinical trials,demonstrating sus-tained wake-promoting effects and favorable safety profiles in patients with NT1,heralding a break-through in pathogenesis-oriented treatment.关键词
发作性睡病/日间过度嗜睡/促觉醒药物Key words
narcolepsy/excessive daytime sleepi-ness/wake-promoting agents分类
医药卫生引用本文复制引用
詹淑琴,张慧敏,张益萌..促觉醒药物治疗发作性睡病研究进展[J].中国临床药理学与治疗学,2025,30(12):1615-1624,10.基金项目
国家自然科学基金(82371489) （82371489）
国家重点研发计划项目(2021YFC2501400) （2021YFC2501400）
