Orexin receptors: possible therapeutic targets for psychiatric disorders.

IF 3.3 3区医学 Q2 NEUROSCIENCES

Psychopharmacology Pub Date : 2025-08-01 Epub Date: 2025-03-28 DOI:10.1007/s00213-025-06767-1

Shigeyuki Chaki

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引用次数: 0

Abstract

Rationale: Orexins, comprising orexin-A and orexin-B, are neuropeptides with extensive projections throughout the central nervous system. They are implicated in a variety of physiological processes through their receptors, orexin type 1 (OX₁) and orexin type 2 (OX₂) receptors. Among the physiological functions of orexins, their role in sleep/wake regulation has garnered significant attention. Consequently, three orexin receptor antagonists that block both OX₁ and OX₂ receptors (dual orexin receptor antagonist; DORA) are available on the market for the treatment of insomnia. Additionally, another DORA, vornorexant, has been submitted for approval.

Objective: Beyond sleep disorders, the orexin system is deeply implicated in the pathophysiology of several psychiatric disorders, including depression, anxiety, and substance use disorders.

Results: Accumulating evidence indicates that orexin receptor antagonists improve behavioral abnormalities that mimic certain psychiatric disorders in animal models and are effective in treating these disorders or their symptoms in humans. Moreover, orexin receptor antagonists are expected not only to alleviate core symptoms of psychiatric disorders but also to improve sleep disturbances, which are often comorbid with these conditions.

Conclusion: Drug discovery and development targeting orexin receptors should provide novel therapeutic options for the treatment of psychiatric disorders.

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食欲素受体：精神疾病可能的治疗靶点。

原理：食欲素是一种神经肽，由食欲素a和食欲素b组成，在整个中枢神经系统中具有广泛的投射。它们通过它们的受体，食欲素1型（OX1）和食欲素2型（OX2）受体参与多种生理过程。在食欲素的生理功能中，它们在睡眠/觉醒调节中的作用引起了人们的极大关注。因此，三种同时阻断OX1和OX2受体的食欲素受体拮抗剂(双重食欲素受体拮抗剂；市面上都有治疗失眠的药物。此外，另一个DORA， vornorexant，已提交审批。目的：除了睡眠障碍外，食欲素系统还与多种精神疾病的病理生理学密切相关，包括抑郁、焦虑和物质使用障碍。结果：越来越多的证据表明，食欲素受体拮抗剂改善了动物模型中模仿某些精神疾病的行为异常，并且对治疗这些疾病或其在人类中的症状有效。此外，食欲素受体拮抗剂不仅有望缓解精神疾病的核心症状，而且还有望改善睡眠障碍，这通常是这些疾病的合并症。结论：以食欲素受体为靶点的药物的发现和开发将为精神疾病的治疗提供新的选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Psychopharmacology 医学-精神病学

CiteScore

7.10

自引率

5.90%

发文量

257

审稿时长

2-4 weeks

期刊介绍： Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.