Department of Molecular Neuroscience and Integrative Physiology, Faculty of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8640, Japan.
CNS Drugs. 2013 Feb;27(2):83-90. doi: 10.1007/s40263-012-0036-8.
Orexin A and orexin B are hypothalamic neuropeptides initially identified as endogenous ligands for two orphan G-protein coupled receptors (GPCRs). They play critical roles in the maintenance of wakefulness by regulating function of monoaminergic and cholinergic neurons that are implicated in the regulation of wakefulness. Loss of orexin neurons in humans is associated with narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and cataplexy, further suggesting the particular importance of orexin in the maintenance of the wakefulness state. These findings have encouraged pharmaceutical companies to develop drugs targeting orexin receptors as novel medications of sleep disorders, such as narcolepsy and insomnia. Indeed, phase III clinical trials were completed last year of suvorexant, a non-selective (dual) antagonist for orexin receptors, for the treatment of primary insomnia, and demonstrate promising results. The New Drug Application (NDA) for suvorexant has been submitted to the US FDA. Thus, the discovery of a critical role played by the orexin system in the regulation of sleep/wakefulness has opened the door of a new era for sleep medicine.
食欲素 A 和食欲素 B 是下丘脑神经肽，最初被鉴定为两种孤儿 G 蛋白偶联受体（GPCR）的内源性配体。它们通过调节与觉醒调节有关的单胺能和胆碱能神经元的功能，在维持觉醒中发挥关键作用。人类食欲素神经元的丧失与嗜睡症有关，嗜睡症是一种以日间过度嗜睡和猝倒为特征的睡眠障碍，这进一步表明了食欲素在维持觉醒状态中的特殊重要性。这些发现促使制药公司开发靶向食欲素受体的药物，作为治疗嗜睡症和失眠等睡眠障碍的新型药物。事实上，去年完成了苏沃雷生（suvorexant）的 III 期临床试验，苏沃雷生是一种非选择性（双）食欲素受体拮抗剂，用于治疗原发性失眠，并取得了有希望的结果。苏沃雷生的新药申请（NDA）已提交给美国 FDA。因此，食欲素系统在调节睡眠/觉醒中的关键作用的发现为睡眠医学开辟了一个新时代。
