Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jan 6;57:509-533.
doi: 10.1146/annurev-pharmtox-010716-104837.

The Discovery of Suvorexant, the First Orexin Receptor Drug for Insomnia


The Discovery of Suvorexant, the First Orexin Receptor Drug for Insomnia

Paul J Coleman et al. Annu Rev Pharmacol Toxicol. .


Historically, pharmacological therapies have used mechanisms such as γ-aminobutyric acid A (GABAA) receptor potentiation to drive sleep through broad suppression of central nervous system activity. With the discovery of orexin signaling loss as the etiology underlying narcolepsy, a disorder associated with hypersomnolence, orexin antagonism emerged as an alternative approach to attenuate orexin-induced wakefulness more selectively. Dual orexin receptor antagonists (DORAs) block the activity of orexin 1 and 2 receptors to both reduce the threshold to transition into sleep and attenuate orexin-mediated arousal. Among DORAs evaluated clinically, suvorexant has pharmacokinetic properties engineered for a plasma half-life appropriate for rapid sleep onset and maintenance at low to moderate doses. Unlike GABAA receptor modulators, DORAs promote both non-rapid eye movement (NREM) and REM sleep, do not disrupt sleep stage-specific quantitative electroencephalogram spectral profiles, and allow somnolence indistinct from normal sleep. The preservation of cognitive performance and the ability to arouse to salient stimuli after DORA administration suggest further advantages over historical therapies.

Keywords: hyperarousal; insomnia; orexin receptor antagonists; orexins; sleep; suvorexant.

Similar articles

See all similar articles

Cited by 18 articles

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources