Orexin Receptors: Pharmacology and Therapeutic Opportunities

Annual Review of Pharmacology and Toxicology - Tập 51 Số 1 - Trang 243-266 - 2011
Thomas E. Scammell1, Christopher J. Winrow2
1Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. [email protected]
2Neuroscience Department, Merck Research Laboratories, West Point, Pennsylvania 19486;

Tóm tắt

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.

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Annual Review of Pharmacology and Toxicology

Tập 51 Số 1

243-266

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