摘要
Abstract
Sleep-wake regulation is a core physio-logical process dominated by widely distributed neural circuits in the brain.In recent years,with the development of optogenetics and chemogenet-ics technologies,researchers have not only im-proved their understanding of the functions of mul-tiple classic regulatory brain regions(such as the re-ticular activating system,thalamus,hypothalamus,and basal forebrain)but also successively identified and verified a series of novel sleep-wake regulatory nuclei.These studies have simultaneously revealed the regulatory roles of various neurotransmitters,including histamine(HA),dopamine(DA),orexin,γ-aminobutyric acid(GABA),and norepinephrine(NE),in the sleep-wake process,laying a theoretical foundation for deciphering the mechanisms of sleep-wake-related neural circuits.This article sys-tematically reviews the research progress on the neural mechanisms of sleep-wake regulation,ex-plores its intervention targets,and provides a theo-retical basis for the development of novel wake-promoting drugs.Regarding therapeutic targets,drugs such as histamine H3 receptor antagonists(e.g.,pitolisant),dopaminergic modulators(e.g.,modafinil,solriamfetol),orexin type 2 receptor ago-nists(e.g.,TAK-861),GABA B receptor agonists(e.g.,sodium oxybate),and NE reuptake inhibitors(e.g.,AXS-12)have shown broad clinical application prospects in promoting wakefulness.Although the development of wake-promoting drugs still faces challenges such as hepatotoxicity,significant indi-vidual differences in efficacy,and lack of long-term safety data,with the deepening understanding of the mechanisms of sleep-wake-related circuits,pre-cise intervention strategies targeting specific neu-rotransmitter systems are expected to open up new avenues for the treatment of sleep-wake disor-ders.关键词
睡眠-觉醒调控/神经环路/机制/促觉醒药物/治疗靶点Key words
sleep-wake regulation/neural cir-cuits/mechanism/wake-promoting agents/thera-peutic targets分类
医药卫生
