Orexin Receptors: Pharmacology and Therapeutic Opportunities

Orexin-A and -B (also known as hypocretin-1 and -2) are neuropeptides produced in the lateral hypothalamus that promote many aspects of arousal through the OX1 and OX2 receptors. In fact, they are necessary for normal wakefulness, as loss of the orexin-producing neurons causes narcolepsy in humans a...

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Bibliographic Details
Published in:Annual review of pharmacology and toxicology 2011-02, Vol.51 (1), p.243-266
Main Authors: SCAMMELL, Thomas E, WINROW, Christopher J
Format: Article
Language:English
Subjects:
Addictive behaviors
Adult and adolescent clinical studies
Animals
Biological and medical sciences
Disorders of higher nervous function. Focal brain diseases. Central vestibular syndrome and deafness. Brain stem syndromes
Drug addiction
Drug addictions
Drug Design
Humans
Hypnotics and Sedatives - pharmacology
Hypothalamus - metabolism
Intracellular Signaling Peptides and Proteins - metabolism
Medical sciences
Nervous system (semeiology, syndromes)
Neurology
Neuropeptides - metabolism
Orexin Receptors
Orexins
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Receptors, G-Protein-Coupled - antagonists & inhibitors
Receptors, G-Protein-Coupled - metabolism
Receptors, Neuropeptide - antagonists & inhibitors
Receptors, Neuropeptide - metabolism
Sleep Initiation and Maintenance Disorders - drug therapy
Sleep Initiation and Maintenance Disorders - physiopathology
Toxicology
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Summary:Orexin-A and -B (also known as hypocretin-1 and -2) are neuropeptides produced in the lateral hypothalamus that promote many aspects of arousal through the OX1 and OX2 receptors. In fact, they are necessary for normal wakefulness, as loss of the orexin-producing neurons causes narcolepsy in humans and rodents. This has generated considerable interest in developing small-molecule orexin receptor antagonists as a novel therapy for the treatment of insomnia. Orexin antagonists, especially those that block OX2 or both OX1 and OX2 receptors, clearly promote sleep in animals, and clinical results are encouraging: Several compounds are in Phase III trials. As the orexin system mainly promotes arousal, these new compounds will likely improve insomnia without incurring many of the side effects encountered with current medications.
ISSN:0362-1642
1545-4304
DOI:10.1146/annurev-pharmtox-010510-100528