睡眠调控与睡眠调节药物研究进展

Research progress in sleep regulation and sleep modulating agents

本文以“双过程模型”和“跷跷板开关模型”为主线,评述睡眠医学基础研究的理论框架。“睡眠发生系统(促睡眠神经元)”和“觉醒发生系统(促觉醒神经元)”之间的相互抑制性调节通路,为睡眠和觉醒交替提供了解剖学结构基础。昼夜节律对睡眠和觉醒转换提供“定时服务”,内稳态平衡对其提供“驱动力”。在睡眠医学科学理论研究的助推下,基于新机制、作用于新靶点的多种新型睡眠调节药物陆续进入临床,主要分为促眠药和促醒药,作用于γ-氨基丁酸系统、褪黑素系统、促食欲素系统、组胺系统和单胺系统发挥对睡眠疾病的治疗作用。剖析睡眠-觉醒的神经调控机制,把握睡眠疾病治疗药物的研究动态,可为睡眠疾病的病因学和治疗学研究提供参考。

In this review, the theoretical framework of sleep neurobiology based on the "dual-process model" and the "flip-flop switch model" is explained. The mutual inhibitory pathways between the sleep-promoting and the wake-promoting systems provide an anatomical basis for the alternation of sleep and wakefulness. The circadian rhythm provides the "timing service" for the sleep-wake transition, while homeostasis serves as the "driving force". With the development of theoretical research on sleep medicines, a variety of new drugs acting on novel targets and mechanisms have been used in the clinical treatment of sleep disorders. The pharmacological mechanisms of these new drugs are associated with the functional modulation in various neurochemicals including γ-aminobutyric acid,melatonin, orexin, histamine and monoamine systems. Together, the advancement of sleep research and the development of new drugs have important implications for the etiology and treatment of sleep disorders.