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The hypocretin/orexin system in sleep disorders: preclinical insights and clinical progress

Authors Chow M, Cao M

Received 31 October 2015

Accepted for publication 2 February 2016

Published 14 March 2016 Volume 2016:8 Pages 81—86

DOI https://doi.org/10.2147/NSS.S76711

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Prof. Dr. Roumen Kirov

Peer reviewer comments 4

Editor who approved publication: Professor Steven Shea

Matthew Chow, Michelle Cao

Department of Psychiatry and Behavioral Sciences, Division of Sleep Medicine, Stanford University School of Medicine, Stanford, CA, USA

Abstract: Much of the understanding of the hypocretin/orexin (HCRT/OX) system in sleep–wake regulation came from narcolepsy–cataplexy research. The neuropeptides hypocretin-1 and -2/orexin-A and -B (HCRT-1 and -2/OX-A and -B, respectively), as we know, are intimately involved in the regulation wakefulness. The HCRT/OX system regulates sleep–wake control through complex interactions between monoaminergic/cholinergic (wake-promoting) and gamma-aminobutyric acid-ergic (sleep-promoting) neuronal systems. Deficiency of HCRT/OX results in loss of sleep–wake control or stability with consequent unstable transitions between wakefulness to nonrapid eye movement and rapid eye movement sleep. This manifests clinically as abnormal daytime sleepiness with sleep attacks and cataplexy. Research on the development of HCRT/OX agonists and antagonists for the treatment of sleep disorders has dramatically increased with the US Food and Drug Administration approval of the first-in-class dual HCRT/OX receptor antagonist for the treatment of insomnia. This review focuses on the origin, mechanisms of HCRT/OX receptors, clinical progress, and applications for the treatment of sleep disorders.

Keywords: hypocretin, orexin, narcolepsy, insomnia, orexin antagonist, orexin agonist

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