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Published on: November 15, 2013
Selective orexin receptor antagonists
Terry P Lebold1, Pascal Bonaventure, Brock T Shireman
1Janssen Research & Development, 3210 Merryfield Row, San Diego, CA 92121, USA.
Abstract:
The orexin, or hypocretin, neuropeptides (orexin-A and orexin-B) are produced on neurons in the hypothalamus which project to key areas of the brain that control sleep-wake states, modulation of food intake, panic, anxiety, emotion, reward and addictive behaviors. These neuropeptides exert their effects on a pair of G-protein coupled receptors termed the orexin-1 (OX1) and orexin-2 (OX2) receptors. Emerging biology suggests the involvement of these receptors in psychiatric disorders as they are thought to play a key role in the regulation of multiple systems. This review is intended to highlight key selective OX1 or OX2 small-molecule antagonists.
Insights
Orexin neuropeptides regulate sleep, appetite, and emotions via OX1 and OX2 receptors. This review highlights selective antagonists for these receptors, crucial for understanding psychiatric disorders.
Area of Science:
- Neuroscience
- Pharmacology
- Psychiatry
Background:
- Orexin (hypocretin) neuropeptides, orexin-A and orexin-B, are synthesized in hypothalamic neurons.
- These neurons project to brain regions controlling sleep-wake cycles, feeding, emotion, and reward.
- Orexin-A and orexin-B mediate their effects through two G-protein coupled receptors: orexin-1 (OX1) and orexin-2 (OX2).
Purpose of the Study:
- To review the emerging role of orexin receptors (OX1 and OX2) in psychiatric disorders.
- To highlight selective small-molecule antagonists targeting OX1 or OX2 receptors.
Main Methods:
- Literature review focusing on the involvement of orexin system in neurological and psychiatric conditions.
- Identification and summary of key selective OX1 and OX2 small-molecule antagonists.
Main Results:
- Orexin receptors are implicated in the regulation of multiple physiological and behavioral systems.
- Emerging evidence suggests a significant role for these receptors in the pathophysiology of psychiatric disorders.
- Development of selective OX1 and OX2 antagonists is a key area of research.
Conclusions:
- The orexin system, through OX1 and OX2 receptors, is a critical regulator of fundamental behaviors.
- Targeting OX1 or OX2 receptors with selective antagonists offers potential therapeutic strategies for psychiatric disorders.
- Further research into orexin receptor modulation is warranted for advancing treatments.
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