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Orexin receptors: possible therapeutic targets for psychiatric disorders

Shigeyuki Chaki1,2

  • 1Taisho Pharmaceutical Co., Ltd, Toshima-Ku, Tokyo, 170-8633, Japan. s-chaki@taisho.co.jp.

Psychopharmacology
|March 28, 2025
PubMed
Abstract

Insights

Orexin receptor antagonists, initially developed for insomnia, show promise in treating psychiatric disorders like depression and anxiety. These drugs may also improve comorbid sleep disturbances in patients with mental health conditions.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Psychiatry

Background:

  • Orexins (orexin-A and orexin-B) are neuropeptides regulating physiological processes via OX1 and OX2 receptors.
  • The orexin system's role in sleep/wake cycles led to dual orexin receptor antagonists (DORAs) for insomnia treatment.
  • Vornorexant is an additional DORA submitted for approval.

Purpose of the Study:

  • To explore the orexin system's involvement in the pathophysiology of psychiatric disorders beyond sleep disorders.
  • To investigate the therapeutic potential of orexin receptor antagonists in conditions such as depression, anxiety, and substance use disorders.

Main Methods:

  • Review of accumulating evidence on orexin receptor antagonists.
  • Analysis of preclinical data from animal models mimicking psychiatric disorders.
  • Evaluation of clinical data on the efficacy of orexin receptor antagonists in human psychiatric conditions.

Main Results:

  • Orexin receptor antagonists demonstrate efficacy in improving behavioral abnormalities in animal models of psychiatric disorders.
  • These antagonists are effective in treating psychiatric disorders or their symptoms in humans.
  • Orexin receptor antagonists are anticipated to alleviate core psychiatric symptoms and comorbid sleep disturbances.

Conclusions:

  • Targeting orexin receptors offers a novel therapeutic strategy for psychiatric disorders.
  • Drug discovery focused on orexin receptors presents new treatment options.
  • Orexin receptor antagonists hold potential for comprehensive management of psychiatric conditions, including associated sleep issues.
Keywords:
DORAOX1 receptor antagonistOX2 receptor antagonistOrexinPsychiatric disorder

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