Orexin receptors in GtoPdb v.2023.1

IUPHAR/BPS Guide to Pharmacology CITE Pub Date : 2023-04-26 DOI:10.2218/gtopdb/f51/2023.1

Gary Aston-Jones, Pascal Bonaventure, Paul Coleman, Luis De Lecea, Debbie Hartman, Daniel Hoyer, Laura Jacobson, Thomas Kilduff, Jyrki P. Kukkonen, Terrence P. McDonald, Rod Porter, John Renger, Takeshi Sakurai, Jerome M Siegel, Gregor Sutcliffe, Neil Upton, Christopher J. Winrow, Masashi Yanagisawa

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Abstract

Orexin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Orexin receptors [43]) are activated by the endogenous polypeptides orexin-A and orexin-B (also known as hypocretin-1 and -2; 33 and 28 aa) derived from a common precursor, preproorexin or orexin precursor, by proteolytic cleavage and some typical peptide modifications [117]. Orexin signaling has been associated with regulation of sleep and wakefulness, reward and addiction, appetite and feeding, pain gating, stress response, anxiety and depression. Currently the orexin receptor ligands in clinical use are the dual orexin receptor antagonists suvorexant and lemborexant and daridorexant, which are used as hypnotics, and several dual and OX2-selective antagonists are under development. Multiple orexin agonists are in development for the treatment of narcolepsy and other sleep disorders. Orexin receptor 3D structures have been solved [146, 144, 55, 126, 47, 109, 7, 145].

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GtoPdb v.2023.1中的食欲素受体

食欲素受体(由NC-IUPHAR食欲素受体小组委员会商定的命名[43])由内源性多肽食欲素- a和食欲素- b(也称为下丘脑分泌素-1和-2;33和28aa)通过蛋白水解裂解和一些典型的肽修饰，由共同的前体，即食欲素前原或食欲素前体衍生而来[117]。食欲素信号与睡眠和清醒、奖励和成瘾、食欲和进食、疼痛门控、压力反应、焦虑和抑郁的调节有关。目前临床使用的食欲素受体配体有双重食欲素受体拮抗剂suvorexant、leborexant和daridorexant，用于催眠，几种双重和ox2选择性拮抗剂正在开发中。多种食欲素激动剂正在开发中，用于治疗嗜睡症和其他睡眠障碍。食欲素受体的三维结构已经被解决[146,144,55,126,47,109,7,145]。

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IUPHAR/BPS Guide to Pharmacology CITE

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