Identification of a Novel Series of Orexin Receptor Antagonists with a Distinct Effect on Sleep Architecture for the Treatment of Insomnia
| العنوان: | Identification of a Novel Series of Orexin Receptor Antagonists with a Distinct Effect on Sleep Architecture for the Treatment of Insomnia |
|---|---|
| المؤلفون: | Chetan Pandit, Christine E. Gee, Daniel Hoyer, Vinod D. Chaudhari, Grit Laue, Juergen Wagner, Laura H. Jacobson, Dirk Behnke, Claudia Betschart, Simona Cotesta, Sangamesh Badiger, Samuel Hintermann, Markus Fendt, Silvio Ofner |
| المصدر: | Journal of Medicinal Chemistry. 56:7590-7607 |
| بيانات النشر: | American Chemical Society (ACS), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, Indoles, Sleep induction, Primary Insomnia, Motor Activity, Pharmacology, Doras, Non-rapid eye movement sleep, Mice, Structure-Activity Relationship, Quinoxalines, Sleep Initiation and Maintenance Disorders, mental disorders, Drug Discovery, medicine, Animals, Spiro Compounds, Sleep Stages, biology, Electromyography, Chemistry, Suvorexant, Electroencephalography, Stereoisomerism, Azepines, Triazoles, biology.organism_classification, Orexin receptor, Mice, Inbred C57BL, Pyrimidines, Molecular Medicine, Orexin Receptor Antagonists, Almorexant, Sleep, medicine.drug |
| الوصف: | Dual orexin receptor (OXR) antagonists (DORAs) such as almorexant, 1 (SB-649868), or suvorexant have shown promise for the treatment of insomnias and sleep disorders in several recent clinical trials in volunteers and primary insomnia patients. The relative contribution of antagonism of OX1R and OX2R for sleep induction is still a matter of debate. We therefore initiated a drug discovery project with the aim of creating both OX2R selective antagonists and DORAs. Here we report that the OX2R selective antagonist 26 induced sleep in mice primarily by increasing NREM sleep, whereas the DORA suvorexant induced sleep largely by increasing REM sleep. Thus, OX2R selective antagonists may also be beneficial for the treatment of insomnia. |
| تدمد: | 1520-4804 0022-2623 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::48dc21e46c9f923dccf5394833956e52 https://doi.org/10.1021/jm4007627 |
| رقم الأكسشن: | edsair.doi.dedup.....48dc21e46c9f923dccf5394833956e52 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15204804 00222623 |
|---|