失眠,通常用苯二氮卓(BZD)受体激动剂治疗,由于相关的严重副作用,如滥用和依赖,提出了挑战。为了解决这些问题,已经进行了许多研究来开发和推进药理学和非药理学干预措施。双重食欲素受体拮抗剂(DORA),其中包括suvorexant,daridorexant和lemborexant,最近已被美国食品和药物管理局(美国FDA)批准作为一种新的药物治疗替代品。与作为γ-氨基丁酸A型亚基α1受体的正变构调节剂的BZD受体激动剂不同,DORAs通过与食欲素受体1型和2型结合起作用,并抑制促觉醒食欲素神经肽的作用。这些药物诱导正常睡眠而不改变睡眠阶段,不要损害注意力和记忆力,并促进更容易的觉醒。然而,需要更多真实的安全信息。选择性食欲素-2受体拮抗剂(2-SORA)正在临床开发中。这篇综述概述了与失眠有关的作用机制,药代动力学,DORA和SORA的疗效和安全性信息。根据失眠管理指南,慢性失眠症的一线治疗是失眠症的认知行为疗法(CBT-I).尽管它已被证明可以有效改善与睡眠相关的生活质量,由于面对面格式,它有几个限制限制。最近,Somryst®等数字处方疗法已获得美国FDA批准。Somryst®,基于智能手机应用的CBT-I,在患者中表现出有意义的反应。然而,数字限制可能会影响可扩展性。总的来说,这些发展为失眠治疗提供了有希望的替代方案,强调安全,功效,和可访问性。
Insomnia, commonly treated with benzodiazepine (BZD) receptor agonists, presents challenges due to associated serious side effects such as abuse and dependence. To address these concerns, many researches have been conducted to develop and advance both pharmacological and non-pharmacological interventions. Dual orexin receptor antagonists (DORAs), which include suvorexant, daridorexant and lemborexant, have recently been approved by United States Food and Drug Administration (US FDA) as a novel pharmacotherapeutic alternative. Unlike BZD receptor agonists that act as positive allosteric modulators of the gamma-aminobutyric acid type A subunit alpha 1 receptor, DORAs function by binding to both orexin receptor types 1 and 2, and inhibiting the action of the wake-promoting orexin neuropeptide. These drugs induce normal sleep without sleep stage change, do not impair attention and memory performance, and facilitate easier awakening. However, more real-world safety information is needed. Selective orexin-2 receptor antagonists (2-SORAs) is under clinical developments. This review provides an overview of the mechanism of action in relation to insomnia, pharmacokinetics, efficacy and safety information of DORAs and SORA. According to insomnia management guidelines, the first-line treatment for chronic insomnia is cognitive behavioral therapy for insomnia (CBT-I). Although it has proven effective in improving sleep-related quality of life, it has several restrictions limitations due to a face-to-face format. Recently, prescription digital therapy such as Somryst® was approved by US FDA. Somryst®, a smartphone app-based CBT-I, demonstrated meaningful responses in patients. However, digital limitations may impact scalability. Overall, these developments offer promising alternatives for insomnia treatment, emphasizing safety, efficacy, and accessibility.