Abstract
Actelion Pharmaceuticals achieved clinical proof-of-concept for the treatment of insomnia in 2007 with the release of Phase II data on Almorexant, a potent dual (OX1R/OX2R) orexin receptor antagonist. GlaxoSmithKline also released clinical efficacy data on an orexin receptor antagonist in 2007 for the treatment of insomnia. With these exciting findings, the search for orexin (or hypocretin) receptor antagonists for the treatment of sleep and neurological disorders has recently increased in intensity in the pharmaceutical industry. This review will focus on the medicinal chemistry of orexin antagonists and the potential therapeutic value of this therapy for the treatment of insomnia. Receptor subtype selectivity will also be described to highlight the tools currently available to delineate receptor-specific pharmacology.
Keywords: Orexin, hypocretin, insomnia, almorexant, GPCR, cataplexy, OX1R, OX2R
Current Topics in Medicinal Chemistry
Title: Orexin Receptor Antagonists: Medicinal Chemistry and Therapeutic Potential
Volume: 8 Issue: 11
Author(s): Anthony J. Roecker and Paul J. Coleman
Affiliation:
Keywords: Orexin, hypocretin, insomnia, almorexant, GPCR, cataplexy, OX1R, OX2R
Abstract: Actelion Pharmaceuticals achieved clinical proof-of-concept for the treatment of insomnia in 2007 with the release of Phase II data on Almorexant, a potent dual (OX1R/OX2R) orexin receptor antagonist. GlaxoSmithKline also released clinical efficacy data on an orexin receptor antagonist in 2007 for the treatment of insomnia. With these exciting findings, the search for orexin (or hypocretin) receptor antagonists for the treatment of sleep and neurological disorders has recently increased in intensity in the pharmaceutical industry. This review will focus on the medicinal chemistry of orexin antagonists and the potential therapeutic value of this therapy for the treatment of insomnia. Receptor subtype selectivity will also be described to highlight the tools currently available to delineate receptor-specific pharmacology.
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Cite this article as:
Roecker J. Anthony and Coleman J. Paul, Orexin Receptor Antagonists: Medicinal Chemistry and Therapeutic Potential, Current Topics in Medicinal Chemistry 2008; 8 (11) . https://dx.doi.org/10.2174/156802608784936746
DOI https://dx.doi.org/10.2174/156802608784936746 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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