Journal
JOURNAL OF NEUROGENETICS
Volume 25, Issue 1-2, Pages 52-61Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/01677063.2011.566953
Keywords
hypocretin; insomnia; orexin; pharmacology; therapy; MK-4305
Categories
Ask authors/readers for more resources
Orexins/hypocretins are key neuropeptides responsible for regulating central arousal and reward circuits. Two receptors respond to orexin signaling, orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R) with partially overlapping nervous system distributions. Genetic studies suggest orexin receptor antagonists could be therapeutic for insomnia and other disorders with disruptions of sleep and wake. Suvorexant (MK-4305) is a potent, selective, and orally bioavailable antagonist of OX1R and OX2R currently under clinical investigation as a novel therapy for insomnia. Examination of Suvorexant in radioligand binding assays using tissue from transgenic rats expressing the human OX2R found nearly full receptor occupancy (> 90%) at plasma exposures of 1.1 mu mu M. Dosed orally Suvorexant significantly and dose-dependently reduced locomotor activity and promoted sleep in rats (10, 30, and 100 mg/kg), dogs (1 and 3 mg/kg), and rhesus monkeys (10 mg/kg). Consistent cross-species sleep/wake architecture changes produced by Suvorexant highlight a unique opportunity to develop dual orexin antagonists as a novel therapy for insomnia.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available