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Orexin Receptor Antagonists as Emerging Treatments for Psychiatric Disorders

Ying Han1, Kai Yuan2,3, Yongbo Zheng2

  • 1National Institute of Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, 100191, China.

Neuroscience Bulletin
|November 30, 2019
PubMed

Insights

Orexin receptor antagonists show promise for treating psychiatric disorders. Selective OX2R antagonists and dual antagonists are effective for sleep issues, while selective OX1R antagonists may help with anxiety and addiction.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Psychiatry

Background:

  • Orexins are neuropeptides regulating sleep-wake cycles, feeding, and emotions.
  • Orexin receptors (OX1R and OX2R) are targets for treating various conditions.
  • Suvorexant's approval for insomnia has spurred research into orexin antagonists.

Purpose of the Study:

  • To review recent findings on the orexin system's role in psychiatric disorders.
  • To discuss the efficacy of different orexin receptor antagonists (SORAs, DORAs) in treating these conditions.
  • To explore future clinical applications and challenges of orexin antagonists.

Main Methods:

  • Review of preclinical and clinical evidence on orexin receptor antagonists.
  • Analysis of selective OX1R antagonists (SORA1s), selective OX2R antagonists (SORA2s), and dual OX1/2R antagonists (DORAs).
  • Examination of the orexin system's involvement in sleep disorders, depression, anxiety, and drug addiction.

Main Results:

  • SORA2s and DORAs demonstrate significant efficacy in treating sleep disorders.
  • SORA1s show potential for treating anxiety and drug addiction.
  • The orexin system is implicated in the pathophysiology of several psychiatric disorders.

Conclusions:

  • Orexin receptor antagonists represent a promising therapeutic avenue for psychiatric disorders.
  • Different antagonist profiles (SORA1, SORA2, DORA) offer targeted treatment options.
  • Further research is needed to optimize clinical applications and address challenges.
Keywords:
AnxietyDepressionDrug addictionInsomniaOrexin

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