Nonclinical pharmacology of daridorexant: a new dual orexin receptor antagonist for the treatment of insomnia
| العنوان: | Nonclinical pharmacology of daridorexant: a new dual orexin receptor antagonist for the treatment of insomnia |
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| المؤلفون: | Giorgio Bergamini, Michel A. Steiner, Catherine Roch, Martine Clozel |
| المصدر: | Psychopharmacology |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Pyrrolidines, Insomnia, Daridorexant, Allosteric regulation, Physical dependence, Review, Pharmacology, Doras, Nonclinical, Orexin Receptors, Sleep Initiation and Maintenance Disorders, Dual orexin receptor antagonist, medicine, Humans, Receptor, biology, Mechanism (biology), business.industry, Sleep architecture, Imidazoles, Antagonist, biology.organism_classification, Orexin receptor, Orexin, Orexin Receptor Antagonists, medicine.symptom, Sleep, business |
| الوصف: | Dual orexin receptor antagonists (DORAs) represent a novel type of sleep medication that provide an alternative to the traditionally used positive allosteric gamma-aminobutyric acid (GABA)-A receptor modulators. Daridorexant is a new DORA that exhibited in phase 3 trials in insomnia not only a beneficial effect on sleep variables, measured objectively and assessed subjectively, but also an improvement in daytime functioning. Daridorexant was discovered through a tailored research program aimed at identifying an optimized sleep-promoting molecule with pharmacokinetic properties appropriate for covering the whole night while avoiding next-morning residual activity at efficacious doses. By specific binding to both orexin receptors, daridorexant inhibits the actions of the wake-promoting orexin (also called hypocretin) neuropeptides. This mechanism avoids a more widespread inhibition of neuronal pathways and associated side effects that are intrinsic to positive allosteric GABA-A receptor modulators. Here, we review the general pharmacology of daridorexant, based on nonclinical pharmacology studies of daridorexant, unpublished or already described, or based on work with other DORAs. Some unique features of daridorexant will be highlighted, such as the promotion of natural and surmountable sleep, the preservation of memory and cognition, the absence of tolerance development or risk of physical dependence, and how it can benefit daytime functioning. Supplementary Information The online version contains supplementary material available at 10.1007/s00213-021-05954-0. |
| تدمد: | 1432-2072 0033-3158 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::98223dcb1d64e58042db5b10ea52358eTest https://doi.org/10.1007/s00213-021-05954-0Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....98223dcb1d64e58042db5b10ea52358e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14322072 00333158 |
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