Orexins comprise two neuropeptides produced by orexin neurons in the lateral hypothalamus and are released by extensive projections of these neurons throughout the central nervous system. Orexins bind and activate their associated G protein-coupled orexin type 1 receptors (OX1Rs) and OX2Rs and act on numerous physiological processes, such as sleep-wake regulation, feeding, reward, emotion, and motivation. Research on the development of orexin receptor antagonists has dramatically increased with the approval of suvorexant for the treatment of primary insomnia. In the present review, we discuss recent findings on the involvement of the orexin system in the pathophysiology of psychiatric disorders, including sleep disorders, depression, anxiety, and drug addiction. We discuss the actions of orexin receptor antagonists, including selective OX1R antagonists (SORA1s), selective OX2R antagonists (SORA2s), and dual OX1/2R antagonists (DORAs), in the treatment of these disorders based on both preclinical and clinical evidence. SORA2s and DORAs have more pronounced efficacy in the treatment of sleep disorders, whereas SORA1s may be promising for the treatment of anxiety and drug addiction. We also discuss potential challenges and opportunities for the application of orexin receptor antagonists to clinical interventions.

中文翻译：

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食欲素受体拮抗剂作为精神疾病的新兴治疗方法。


食欲素由下丘脑外侧的食欲素神经元产生的两种神经肽组成，并通过这些神经元在整个中枢神经系统的广泛投射而释放。食欲素结合并激活其相关的 G 蛋白偶联食欲素 1 型受体 (OX1R) 和 OX2R，并作用于许多生理过程，例如睡眠-觉醒调节、进食、奖励、情绪和动机。随着 suvorexant 用于治疗原发性失眠的批准，对食欲素受体拮抗剂开发的研究急剧增加。在本综述中，我们讨论了有关食欲素系统参与精神疾病病理生理学的最新发现，包括睡眠障碍、抑郁、焦虑和药物成瘾。我们根据临床前和临床证据讨论食欲素受体拮抗剂，包括选择性 OX1R 拮抗剂 (SORA1)、选择性 OX2R 拮抗剂 (SORA2) 和双重 OX1/2R 拮抗剂 (DORA) 在治疗这些疾病中的作用。 SORA2 和 DORA 在治疗睡眠障碍方面具有更显着的功效，而 SORA1 可能有望用于治疗焦虑和药物成瘾。我们还讨论了食欲素受体拮抗剂在临床干预中应用的潜在挑战和机遇。