The DOI matches its Crossref record; 143 of the 143 references it cites were found in a registry or an index.
The Discovery of Suvorexant, the First Orexin Receptor Drug for Insomnia
Abstract
Historically, pharmacological therapies have used mechanisms such as γ-aminobutyric acid A (GABA A ) 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 GABA A 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.
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“In AD-related psychosis, this treatment has the potential to remove the neurotoxicity induced by Aβ (Coleman et al., 2017).”
From An update on the novel and approved drugs for Alzheimer disease (2022) · cites this paper as Coleman et al., 2017
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“Apiprazole works to stabilize the dopamine system (DSSs).”
From An update on the novel and approved drugs for Alzheimer disease (2022) · cites this paper as Coleman et al., 2017
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“It helps to improve the reduction of neurite-induced neuropathy.”
From An update on the novel and approved drugs for Alzheimer disease (2022) · cites this paper as Coleman et al., 2017
Citations
Cites
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The neuropeptidergic connectome of C. elegans
Ripoll-Sánchez, L., Watteyne, J., Sun, H., Fernandez, R. W., Taylor, S. R., Weinreb, A., Bentley, B. L., Hammarlund, M., Miller, D. M., Hobert, O., et al. (2023) · Neuron · doi:10.1016/j.neuron.2023.09.043 · Cited by 172
Levendowski, D. J., Ferini‐Strambi, L., Gamaldo, C. E., Cetel, M. B., Rosenberg, R., & Westbrook, P. R. (2017) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.6618 · Cited by 161
Metadata
- Authors
- Coleman, P. J., Gotter, A. L., Herring, W. J., Winrow, C. J., & Renger, J. J.
- Affiliations
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Department of Neuroscience, Merck Research Laboratories, West Point, Pennsylvania 19486
- Department of Clinical Neuroscience, Merck Research Laboratories, West Point, Pennsylvania 19486
- Venue
- Annual Review of Pharmacology and Toxicology
- Publisher
- Annual Reviews
- Published
- 2017-01-06
- Volume
- 57
- Issue
- 1
- Pages
- 509-533
- ISSN
- 0362-1642 (ISSN-L)
- 1545-4304
- OpenAlex
- W2492327128
- Cited by
- 128
- References
- 143
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 18 · 2023: 9 · 2022: 20 · 2021: 13 · 2020: 13 · 2019: 21 · 2018: 9 · 2017: 8
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Annual Review of Pharmacology and Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- suvorexant, orexin receptor antagonists, insomnia, dual orexin receptor antagonists, orexin signaling, narcolepsy, GABA-A receptor agonists, sleep onset, REM sleep, pharmacokinetics, cognitive performance, wakefulness
- MeSH terms
- Sleep Aids, Pharmaceutical, Orexin Receptor Antagonists, Animals, Azepines, Humans, Sleep Initiation and Maintenance Disorders, Triazoles, Protein Structure, Secondary, Drug Discovery, Orexin Receptors
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