Cited by 131Sleep and Wakefulness ResearchSleep and related disordersCircadian rhythm and melatonin

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

Coleman, Paul J., Gotter, Anthony L., Herring, W. Joseph, Winrow, Christopher J., Renger, John J.·2017·Annual Review of Pharmacology and Toxicology

DOI 10.1146/annurev-pharmtox-010716-104837

Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1146/annurev-pharmtox-010716-104837

Cites

143 of 143 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior
Sakurai, T., Amemiya, A., Ishii, M., Matsuzaki, I., Chemelli, R. M., Tanaka, H., Williams, S. C., Richardson, J. A., Kozlowski, G. P., Wilson, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)80949-6 · Cited by 5,501
The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity
de Lecea, L., Kilduff, T. S., Peyron, C., Gao, X.-B., Foye, P. E., Danielson, P. E., Fukuhara, C., Battenberg, E. L. F., Gautvik, V. T., Bartlett, F. S., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.1.322 · Cited by 3,878
Narcolepsy in orexin Knockout Mice
Chemelli, R. M., Willie, J. T., Sinton, C. M., Elmquist, J. K., Scammell, T., Lee, C., Richardson, J. A., Williams, S. C., Xiong, Y., Kisanuki, Y., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)81973-x · Cited by 3,095
Hypothalamic regulation of sleep and circadian rhythms
Saper, C. B., Scammell, T. E., & Lu, J. (2005) · Nature · doi:10.1038/nature04284 · Cited by 2,804
The Sleep Disorder Canine Narcolepsy Is Caused by a Mutation in the Hypocretin (Orexin) Receptor 2 Gene
Lin, L., Faraco, J., Li, R., Kadotani, H., Rogers, W., Lin, X., Qiu, X., de Jong, P. J., Nishino, S., & Mignot, E. (1999) · Cell · doi:10.1016/s0092-8674(00)81965-0 · Cited by 2,613
A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains
Peyron, C., Faraco, J., Rogers, W., Ripley, B., Overeem, S., Charnay, Y., Nevsimalova, S., Aldrich, M., Reynolds, D., Albin, R., et al. (2000) · Nature Medicine · doi:10.1038/79690 · Cited by 2,118
Hypocretin (orexin) deficiency in human narcolepsy
Nishino, S., Ripley, B., Overeem, S., Lammers, G. J., & Mignot, E. (2000) · The Lancet · doi:10.1016/s0140-6736(99)05582-8 · Cited by 1,776
Benzodiazepine Receptor: Demonstration in the Central Nervous System
Möhler, H., & Okada, T. (1977) · Science · doi:10.1126/science.918669 · Cited by 1,709
Differential expression of orexin receptors 1 and 2 in the rat brain
Marcus, J. N., Aschkenasi, C. J., Lee, C. E., Chemelli, R. M., Saper, C. B., Yanagisawa, M., & Elmquist, J. K. (2001) · Journal of Comparative Neurology · doi:10.1002/cne.1190 · Cited by 1,659
Amyloid-β Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle
Kang, J.-E., Lim, M. M., Bateman, R. J., Lee, J. J., Smyth, L. P., Cirrito, J. R., Fujiki, N., Nishino, S., & Holtzman, D. M. (2009) · Science · doi:10.1126/science.1180962 · Cited by 1,565

Show all 143 references

Research works printed but not linked: 3

Kisanuki YY, 2001, Sleep, 24, A22
Sun H, 2013, Sleep, 36, 259
Spira AP, 2013, JAMA Neurol, 70, 1537

Sorted by citations

Clinical trials of new drugs for Alzheimer disease
Huang, L.-K., Chao, S.-P., & Hu, C.-J. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-019-0609-7 · Cited by 702
G protein-coupled receptors: structure- and function-based drug discovery
Yang, D., Zhou, Q., Labroska, V., Qin, S., Darbalaei, S., Wu, Y., Yuliantie, E., Xie, L., Tao, H., Cheng, J., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00435-w · Cited by 684
Circadian rhythm as a therapeutic target
Ruan, W., Yuan, X., & Eltzschig, H. K. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-00109-w · Cited by 518
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
The Accuracy, Night-to-Night Variability, and Stability of Frontopolar Sleep Electroencephalography Biomarkers
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
An update on the novel and approved drugs for Alzheimer disease
Alhazmi, H. A., & Albratty, M. (2022) · Saudi Pharmaceutical Journal · doi:10.1016/j.jsps.2022.10.004 · Cited by 122
Orexin Receptor Antagonists as Emerging Treatments for Psychiatric Disorders
Han, Y., Yuan, K., Zheng, Y., & Lü, L. (2019) · Neuroscience Bulletin · doi:10.1007/s12264-019-00447-9 · Cited by 122
Hypocretins (orexins): The ultimate translational neuropeptides
Jacobson, L. H., Hoyer, D., & de Lecea, L. (2022) · Journal of Internal Medicine · doi:10.1111/joim.13406 · Cited by 113
Clinical pharmacology, efficacy, and safety of orexin receptor antagonists for the treatment of insomnia disorders
Muehlan, C., Vaillant, C., Zenklusen, I., Kraehenbuehl, S., & Dingemanse, J. (2020) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2020.1817380 · Cited by 104
Sleep, chronic pain, and opioid risk for apnea
Marshansky, S., Mayer, P., Rizzo, D., Baltzan, M., Denis, R., & Lavigne, G. J. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.07.014 · Cited by 69
Targeting Orexin Receptors for the Treatment of Insomnia: From Physiological Mechanisms to Current Clinical Evidence and Recommendations
Mogavero, M. P., Silvani, A., Lanza, G., DelRosso, L. M., Ferini‐Strambi, L., & Ferri, R. (2023) · Nature and Science of Sleep · doi:10.2147/nss.s201994 · Cited by 67
Preliminary examination of the orexin system on relapse-related factors in cocaine use disorder
Suchting, R., Yoon, J. H., Miguel, G. G. S., Green, C. E., Weaver, M. F., Vincent, J. N., Fries, G. R., Schmitz, J. M., & Lane, S. D. (2019) · Brain Research · doi:10.1016/j.brainres.2019.146359 · Cited by 60
Orexin receptor antagonists for the treatment of insomnia and potential treatment of other neuropsychiatric indications
Herring, W. J., Roth, T., Krystal, A. D., & Michelson, D. (2019) · Journal of Sleep Research · doi:10.1111/jsr.12782 · Cited by 53
Self-citation
Insomnia in patients with schizophrenia: current understanding and treatment options
Robertson, I. H., Cheung, A., & Fan, X. (2019) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2019.01.016 · Cited by 54
Sleep-wake and arousal dysfunctions in post-traumatic stress disorder: Role of orexin systems
Kaplan, G. B., Lakis, G. A., & Zhoba, H. B. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.05.006 · Cited by 54
The neuropeptide landscape of human prefrontal cortex
Zhong, W., Barde, S. S., Mitsios, N., Ádori, C., Oksvold, P., von Feilitzen, K., O’Leary, L. A., Csiba, L., Hortobágyi, T., Szocsics, P., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2123146119 · Cited by 52
Differential Roles of Each Orexin Receptor Signaling in Obesity
Kakizaki, M., Tsuneoka, Y., Takase, K., Kim, S. J., Choi, J., Ikkyu, A., Abe, M., Sakimura, K., Yanagisawa, M., & Funato, H. (2019) · iScience · doi:10.1016/j.isci.2019.09.003 · Cited by 51
Targeting the orexin/hypocretin system for the treatment of neuropsychiatric and neurodegenerative diseases: From animal to clinical studies
Ten-Blanco, M., Flores, Á., Cristino, L., Pereda-Pérez, I., & Berrendero, F. (2023) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2023.101066 · Cited by 48
MendelVar: gene prioritization at GWAS loci using phenotypic enrichment of Mendelian disease genes
Sobczyk, M., Gaunt, T. R., & Paternoster, L. (2021) · Bioinformatics · doi:10.1093/bioinformatics/btaa1096 · Cited by 37
The Orexin/Hypocretin System, the Peptidergic Regulator of Vigilance, Orchestrates Adaptation to Stress
Jászberényi, M., Thurzó, B., Bagosi, Z., Vécsei, L., & Tanaka, M. (2024) · Biomedicines · doi:10.3390/biomedicines12020448 · Cited by 42
Chronopathophysiological implications of orexin in sleep disturbances and lifestyle-related disorders
Tsuneki, H., Wada, T., & Sasaoka, T. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.12.010 · Cited by 41
Methodology and theoretical basis of forward genetic screening for sleep/wakefulness in mice
Miyoshi, C., Kim, S. J., Ezaki, T., Ikkyu, A., Hotta-Hirashima, N., Kanno, S., Kakizaki, M., Yamada, M., Wakana, S., Yanagisawa, M., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1906774116 · Cited by 40
Orexin Receptor Antagonists and Insomnia
Wu, X., Xue, T., Chen, Z., Wang, Z., & Chen, G. (2022) · Current Psychiatry Reports · doi:10.1007/s11920-022-01357-w · Cited by 40
Optical probing of orexin/hypocretin receptor antagonists
Li, S., Nevárez, N., Giardino, W. J., & de Lecea, L. (2018) · SLEEP · doi:10.1093/sleep/zsy141 · Cited by 37
Adverse Events Due to Insomnia Drugs Reported in a Regulatory Database and Online Patient Reviews: Comparative Study
Borchert, J. S., Wang, B., Ramzanali, M., Stein, A. B., Malaiyandi, L. M., & Dineley, K. E. (2019) · Journal of Medical Internet Research · doi:10.2196/13371 · Cited by 34
Insight Into Reduction of Wakefulness by Suvorexant in Patients With Insomnia: Analysis of Wake Bouts
Svetnik, V., Snyder, E., Tao, P., Scammell, T. E., Roth, T. G., Lines, C., & Herring, W. J. (2017) · SLEEP · doi:10.1093/sleep/zsx178 · Cited by 33
Self-citation
Molecular mechanism of the wake-promoting agent TAK-925
Yin, J., Kang, Y., McGrath, A. P., Chapman, K., Sjodt, M., Kimura, E., Okabe, A., Koike, T., Miyanohana, Y., Shimizu, Y., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30601-3 · Cited by 33
UPLC-MS/MS determination of suvorexant in urine by a simplified dispersive liquid-liquid micro-extraction followed by ultrasound assisted back extraction from solidified floating organic droplets
Iqbal, M., Ezzeldin, E., Khalil, N. Y., Alam, P., & Al-Rashood, K. A. M. (2018) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2018.10.005 · Cited by 33
The hypocretin/orexin system as a target for excessive motivation in alcohol use disorders
Moorman, D. E. (2018) · Psychopharmacology · doi:10.1007/s00213-018-4871-2 · Cited by 31
Early-onset sleep alterations found in patients with amyotrophic lateral sclerosis are ameliorated by orexin antagonist in mouse models
Guillot, S. J., Lang, C., Simonot, M., Beckett, D., Lulé, D. E., Balz, L. T., Knehr, A., Stuart‐Lopez, G., Vercruysse, P., Dieterle, S., et al. (2025) · Science Translational Medicine · doi:10.1126/scitranslmed.adm7580 · Cited by 29
Rice bran extract supplement improves sleep efficiency and sleep onset in adults with sleep disturbance: A randomized, double-blind, placebo-controlled, polysomnographic study
Um, M. Y., Yang, H., Han, J. K., Kim, J. Y., Kang, S. W., Yoon, M., Kwon, S., & Cho, S. (2019) · Scientific Reports · doi:10.1038/s41598-019-48743-8 · Cited by 28
Translational approaches to influence sleep and arousal
Brown, R. E., Spratt, T. J., & Kaplan, G. B. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.05.002 · Cited by 31
Distinct effects of orexin receptor antagonist and GABA A agonist on sleep and physical/cognitive functions after forced awakening
Seol, J., Fujii, Y., Park, I., Suzuki, Y., Kawana, F., Yajima, K., Fukusumi, S., Okura, T., Satoh, M., Tokuyama, K., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1907354116 · Cited by 28
Effect of gabapentin on sleep and delta and theta EEG power in adult rats exposed to chronic intermittent ethanol vapor and protracted withdrawal during adolescence
Ehlers, C. L., Sánchez-Alavez, M., & Wills, D. N. (2018) · Psychopharmacology · doi:10.1007/s00213-018-4888-6 · Cited by 28
Effect of suvorexant on event-related oscillations and EEG sleep in rats exposed to chronic intermittent ethanol vapor and protracted withdrawal
Sánchez-Alavez, M., Benedict, J., Wills, D. N., & Ehlers, C. L. (2019) · SLEEP · doi:10.1093/sleep/zsz020 · Cited by 26
Orexins and primary headaches: an overview of the neurobiology and clinical impact
Stanyer, E. C., Hoffmann, J., & Holland, P. R. (2024) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2024.2328728 · Cited by 27
Targeting the Orexin System for Prescription Opioid Use Disorder
Matzeu, A., & Martin‐Fardon, R. (2020) · Brain Sciences · doi:10.3390/brainsci10040226 · Cited by 25
The dual orexinergic receptor antagonist DORA-22 improves the sleep disruption and memory impairment produced by a rodent insomnia model
Gamble, M. C., Katsuki, F., McCoy, J. G., Strecker, R. E., & McKenna, J. T. (2019) · SLEEP · doi:10.1093/sleep/zsz241 · Cited by 24
Pharmacokinetics and Pharmacodynamics of the Dual Orexin Receptor Antagonist Daridorexant in Japanese and Caucasian Subjects
Muehlan, C., Zuiker, R. G. J. A., Peeters, P. A. M., Rowles, R., & Dingemanse, J. (2020) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000001182 · Cited by 25
Pharmacological treatment for insomnia in patients with major depressive disorder
Brietzke, E. M., Vázquez, G. H., Kang, M. J. Y., & Soares, C. N. (2019) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2019.1614562 · Cited by 25
Safety, Tolerability, and Pharmacokinetics of Suvorexant: A Randomized Rising-Dose Trial in Healthy Men
Yee, K. L., McCrea, J. B., Panebianco, D. L., Liu, W., Lewis, N. M., Cabalu, T. D., Ramael, S., & Wrishko, R. E. (2018) · Clinical Drug Investigation · doi:10.1007/s40261-018-0650-4 · Cited by 24
Reciprocal relationships between sleep and smell
Gaeta, G., & Wilson, D. A. (2022) · Frontiers in Neural Circuits · doi:10.3389/fncir.2022.1076354 · Cited by 26
Different doses of dual orexin receptor antagonists in primary insomnia: a Bayesian network analysis
Xue, T., Wu, X., Li, J., Chen, S., Wang, Z., Tan, X., Wang, Z., & Zhang, J. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1175372 · Cited by 22
Emerging and upcoming therapies in insomnia
Kim, W.-J., & Kim, H.-S. (2024) · Translational and Clinical Pharmacology · doi:10.12793/tcp.2024.32.e5 · Cited by 23
Effect of CYP3A Inhibition and Induction on the Pharmacokinetics of Suvorexant: Two Phase I, Open-Label, Fixed-Sequence Trials in Healthy Subjects
Wrishko, R. E., McCrea, J. B., Yee, K. L., Liu, W., Panebianco, D. L., Mangin, E. C., Chakravarthy, M. V., Cantarin, M. P. M., & Kraft, W. K. (2019) · Clinical Drug Investigation · doi:10.1007/s40261-019-00764-x · Cited by 21
How well can a large number of polysomnography sleep measures predict subjective sleep quality in insomnia patients?
Svetnik, V., Snyder, E., Tao, P., Roth, T. G., Lines, C., & Herring, W. J. (2019) · Sleep Medicine · doi:10.1016/j.sleep.2019.08.020 · Cited by 20
Self-citation
The Black Book of Psychotropic Dosing and Monitoring
DeBattista, C., & Schatzberg, A. F. (2025) · Psychopharmacology Bulletin · doi:10.64719/pb.4493 · Cited by 23
Circadian regulation of microglia function: Potential targets for treatment of Parkinson’s Disease
Kou, L., Chi, X., Sun, Y., Yin, S., Wu, J., Zou, W., Wang, Y., Jin, Z., Huang, J., Xiong, N., et al. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102232 · Cited by 21
Role of medial hypothalamic orexin system in panic, phobia and hypertension
de Abreu, A. R. R., Molosh, A. I., Johnson, P. L., & Shekhar, A. (2018) · Brain Research · doi:10.1016/j.brainres.2018.09.010 · Cited by 20
Readjustment of circadian clocks by exercise intervention is a potential therapeutic target for sleep disorders: a narrative review
Lee, K., Hong, K., Park, J., & Park, W. (2024) · Physical Activity and Nutrition · doi:10.20463/pan.2024.0014 · Cited by 20
The neuropeptidergic connectome of C. elegansPreprint
Ripoll-Sánchez, L., Watteyne, J., Sun, H., Fernandez, R. W., Taylor, S. R., Weinreb, A., Hammarlund, M., Miller, D. M., Hobert, O., Beets, I., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.10.30.514396 · Cited by 21
Sleep disturbance in substance use disorders: the orexin (hypocretin) system as an emerging pharmacological target
Gyawali, U., & James, M. H. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-022-01404-3 · Cited by 17
Neurophysiology and Treatment of Disorders of Consciousness Induced by Traumatic Brain Injury: Orexin Signaling as a Potential Therapeutic Target
Tang, H., Zhu, Q., Li, W., Qin, S., Gong, Y., Wang, H., Shioda, S., Li, S., Huang, J., Liu, B., et al. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666191029101830 · Cited by 17
A combinatorial target screening strategy for deorphaning macromolecular targets of natural product
Wei, H., Guan, Y., Zhang, L., Liu, S., Lü, A., Cheng, Y., & Cao, D. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112644 · Cited by 17
Induction of narcolepsy-like symptoms by orexin receptor antagonists in mice
Kaushik, M. K., Aritake, K., Chérasse, Y., Imanishi, A., Kanbayashi, T., Urade, Y., & Yanagisawa, M. (2021) · SLEEP · doi:10.1093/sleep/zsab043 · Cited by 17
Palatable food self-administration and reinstatement are not affected by dual orexin receptor antagonism
Khoo, S. Y., Clemens, K. J., & McNally, G. P. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.06.028 · Cited by 17
Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation of 1,4-Diazepan-5-ones
Sercel, Z. P., Sun, A. W., & Stoltz, B. M. (2019) · Organic Letters · doi:10.1021/acs.orglett.9b03530 · Cited by 16
Hypocretin (Orexin) Replacement Therapies
Seigneur, E. M., & de Lecea, L. (2020) · Medicine in Drug Discovery · doi:10.1016/j.medidd.2020.100070 · Cited by 16
Essential structure of orexin 1 receptor antagonist YNT-707, Part II: Drastic effect of the 14-hydroxy group on the orexin 1 receptor antagonistic activity
Ohrui, S., Yamamoto, N., Saitoh, T., Kutsumura, N., Nagumo, Y., Irukayama‐Tomobe, Y., Ogawa, Y., Ishikawa, Y., Watanabe, Y., Hayakawa, D., et al. (2017) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2017.12.069 · Cited by 15
Effects of Bedtime Dosing With Suvorexant and Zolpidem on Balance and Psychomotor Performance in Healthy Elderly Participants During the Night and in the Morning
Bland, H., Li, X., Mangin, E. C., Yee, K. L., Lines, C., Herring, W. J., & Gillespie, G. (2021) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000001439 · Cited by 15
Self-citation
Network pharmacology and pharmacological evaluation for deciphering novel indication of Sishen Wan in insomnia treatment
Wang, L., Zhao, Q., Zhang, Y., Xue, R., Li, S., Li, Y., Yu, J., Li, J., & Zhang, Y.-Z. (2022) · Phytomedicine · doi:10.1016/j.phymed.2022.154500 · Cited by 15
Comparison of polysomnography in people with Alzheimer's disease and insomnia versus non-demented elderly people with insomnia
Tao, P., Svetnik, V., Bliwise, D. L., Zammit, G. K., Lines, C., & Herring, W. J. (2022) · Sleep Medicine · doi:10.1016/j.sleep.2022.11.027 · Cited by 16
Self-citation
The dual orexin/hypocretin receptor antagonist suvorexant reduces addiction-like behaviors for the opioid fentanylPreprint
O’Connor, S. L., Fragale, J. E. C., James, M. H., & Aston‐Jones, G. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.25.061887 · Cited by 15
Circadian Mechanisms in Medicine
Lin, H. Y.-H., Yang, M.-Y., & Lin, S.-F. (2021) · New England Journal of Medicine · doi:10.1056/nejmc2104154 · Cited by 19
Pharmacological interventions targeting α-synuclein aggregation triggered REM sleep behavior disorder and early development of Parkinson's disease
Du, L., He, X., Fan, X., Wei, X., Xu, L., Liang, T., Wang, C., Ke, Y., & Yung, W. (2023) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2023.108498 · Cited by 15
Discovery and first-time disclosure of CVN766, an exquisitely selective orexin 1 receptor antagonist
Glen, A., Bürli, R. W., Livermore, D. G., Buffham, W. J., Merison, S., Rowland, A., Newman, R., Fieldhouse, C., Miller, D. J., Dawson, L. A., et al. (2024) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2024.129629 · Cited by 13
The dual orexin receptor antagonist almorexant blocks the sleep-disrupting and daytime stimulant effects of methamphetamine in rhesus monkeys
Berro, L. F., Moreira-Junior, E. D. C., & Rowlett, J. K. (2021) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2021.108930 · Cited by 12
Residual effects of low dose of suvorexant, zolpidem, and ramelteon in healthy elderly subjects: A randomized double‐blind study
Uemura, S. I., Imanishi, A., Terui, Y., Park, I., Satake, M., Han, G., Shioya, T., Kanbayashi, T., & Nishino, S. (2022) · Neuropsychopharmacology Reports · doi:10.1002/npr2.12262 · Cited by 12
CYP450-Mediated metabolism of suvorexant and investigation of metabolites in forensic case specimens
Skillman, B. N., & Kerrigan, S. (2020) · Forensic Science International · doi:10.1016/j.forsciint.2020.110307 · Cited by 11
A Comprehensive Review of Lemborexant to Treat Insomnia
Fuller, M. C., Carlson, S. F., Grant, C., Berry, V., Ivancich, M. S., Cornett, E. M., Kaye, A. M., Viswanath, O., Urits, I., Shekoohi, S., et al. (2025) · Psychopharmacology Bulletin · doi:10.64719/pb.4483 · Cited by 11
Preclinical pharmacological profiles of vornorexant, a novel potent dual orexin receptor antagonist
Hikichi, H., Tokumaru, Y., Taruta, A., Konno, Y., Karasawa, J.-I., Fukumoto, K., Marumo, T., Fujii, Y., Takahashi, T., Yoshimizu, T., et al. (2025) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/j.jpet.2025.103624 · Cited by 11
Essential structure of orexin 1 receptor antagonist YNT-707, part III: Role of the 14-hydroxy and the 3-methoxy groups in antagonistic activity toward the orexin 1 receptor in YNT-707 derivatives lacking the 4,5-epoxy ring
Yamamoto, N., Ohrui, S., Okada, T., Saitoh, T., Kutsumura, N., Nagumo, Y., Irukayama‐Tomobe, Y., Ogawa, Y., Ishikawa, Y., Watanabe, Y., et al. (2019) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2019.03.010 · Cited by 11
Effect of Gabapentin on Sleep and Event‐Related Oscillations (EROs) in Rats Exposed to Chronic Intermittent Ethanol Vapor and Protracted Withdrawal
Sánchez-Alavez, M., Wills, D. N., Amodeo, L. R., & Ehlers, C. L. (2017) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.13588 · Cited by 10
Dual orexin receptor blocker suvorexant attenuates hypercapnic ventilatory augmentation in mice
Fukushi, I., Yokota, S., Takeda, K., Terada, J., Umeda, A., Yoshizawa, M., Kono, Y., Hasebe, Y., Onimaru, H., Pokorski, M., et al. (2022) · Brain Research · doi:10.1016/j.brainres.2022.148061 · Cited by 11
Pivotal role of orexin signaling in the posterior paraventricular nucleus of the thalamus during the stress-induced reinstatement of oxycodone-seeking behavior
Illenberger, J. M., Flores‐Ramirez, F. J., Pascasio, G., Franco, M., Mendonsa, B., & Martin‐Fardon, R. (2024) · Journal of Psychopharmacology · doi:10.1177/02698811241260989 · Cited by 9
Construction of five- and seven-membered rings facilitated by alkyne–azide functionality: access to quinoline fused triazolo-azepines
Kumar, V. B., Panchal, J. R., Sharma, V., Sharma, S., Sharma, P., & Singh, V. (2024) · Organic & Biomolecular Chemistry · doi:10.1039/d4ob01442a · Cited by 9
The Dual Orexin Receptor Antagonist DORA-22 Improves Mild Stress-induced Sleep Disruption During the Natural Sleep Phase of Nocturnal Rats
Gamble, M. C., Katsuki, F., McCoy, J. G., Strecker, R. E., & McKenna, J. T. (2021) · Neuroscience · doi:10.1016/j.neuroscience.2021.03.003 · Cited by 8
Design and synthesis of novel orexin 2 receptor agonists based on naphthalene skeleton
Hino, T., Saitoh, T., Nagumo, Y., Yamamoto, N., Kutsumura, N., Irukayama‐Tomobe, Y., Ishikawa, Y., Tanimura, R., Yanagisawa, M., & Nagase, H. (2021) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2022.128530 · Cited by 9
From orexin receptor agonist YNT-185 to novel antagonists with drug-like properties for the treatment of insomnia
Mezeiová, E., Janočková, J., Konecny, J., Kobrlová, T., Benková, M., Doležal, R., Prchal, L., Karasova-Zdarova, J., Soukup, O., & Korábečný, J. (2020) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2020.104179 · Cited by 8
Emerging medications and pharmacological treatment approaches for substance use disorders
Raymond, J. S., Athanasopoulos, A. G., Badolato, C. J., Doolan, T. M., Scicluna, R. L., Everett, N. A., Bowen, M. T., & James, M. H. (2024) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2024.173952 · Cited by 9
The association between serum orexin A and short‐term neurological improvement in patients with mild to moderate acute ischemic stroke
Hu, S., Ren, L., Wang, Y., Lei, Z., Cai, J., & Pan, S. (2022) · Brain and Behavior · doi:10.1002/brb3.2845 · Cited by 7
Pharmacokinetics, Pharmacodynamic, Safety and Tolerability of Fazamorexant, a Novel Dual Orexin Receptor Antagonist: Report of the First-in-Human Study
Ni, J., Lu, J., Zhao, D., Zhang, W., Li, B., Huang, X., & Hao, X. (2025) · Drug Design Development and Therapy · doi:10.2147/dddt.s501111 · Cited by 7
Orexin Receptor Antagonists and Insomnia
Saibaba, J., & Sugumaran, R. (2025) · Sleep and Vigilance · doi:10.1007/s41782-025-00320-y · Cited by 7
Efficacy and safety of insomnia pharmacotherapies: Convergent evidence from Bayesian network meta-regression and FAERS-based disproportionality analysis
Liu, H., Wang, Y., Li, M., Liu, X., Chen, X., Zhu, B., & Wang, H. (2025) · Sleep Medicine · doi:10.1016/j.sleep.2025.106848 · Cited by 7
Dual orexin receptor antagonist ameliorates sleep deprivation-induced learning and memory impairment in APP/PS1 mice
Li, Y., Yan, Z., Shao, N., Tang, S. H., Zhang, X., Liu, X. M., & Tang, J. (2024) · Sleep Medicine · doi:10.1016/j.sleep.2024.07.023 · Cited by 7
Discovery of Hypocretin/Orexin Ushers in a New Era of Sleep Research
Prober, D. A. (2018) · Trends in Neurosciences · doi:10.1016/j.tins.2017.11.007 · Cited by 7
Sleep modulating agents
Choi, Y., & Raymer, B. K. (2019) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2019.06.043 · Cited by 7
Updates and confounding factors in delayed sleep–wake phase disorder
Wu, A. (2023) · Sleep and Biological Rhythms · doi:10.1007/s41105-023-00454-4 · Cited by 7
Effect of short-term mindfulness-based stress reduction on sleep quality in male patients with alcohol use disorder
Wang, Y., Chen, C., Gu, L., Zhai, Y., Sun, Y., Gao, G., Xu, Y., Pang, L., & Xu, L.-Y. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.928940 · Cited by 6
The importance of ligand gated ion channels in sleep and sleep disorders
Arnold, E. C., Soler-Llavina, G. J., Kambara, K., & Bertrand, D. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115532 · Cited by 7
Characteristics of psychiatric patients with nightmares after suvorexant administration: A retrospective study
Yasuda, K., Hirano, Y., Takeda, R., Ikeda, R., & Ishida, Y. (2024) · Neuropsychopharmacology Reports · doi:10.1002/npr2.12506 · Cited by 5
Pharmacological Characteristics of Porcine Orexin 2 Receptor and Mutants
Liu, M., Min, T., Zhang, H., Liu, Y., & Wang, Z. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00132 · Cited by 5
Insomnia and hypertension: A misty landscape
Stavropoulos, K., Imprialos, K. P., Doumas, M. N., Karagiannis, A. I., & Papademetriou, V. (2019) · Journal of Clinical Hypertension · doi:10.1111/jch.13519 · Cited by 6
Interaction between the Human OX2 Orexin Receptor and Suvorexant and Some of Its Analogues: SAPT (DFT) Interaction Energy Decomposition Analysis
Farrokhpour, H., Bamdad, F., & Ashrafizaadeh, M. (2022) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.2c02537 · Cited by 4
Pyrazole derivatives as selective orexin-2 receptor antagonists (2-SORA): synthesis, structure–activity–relationship, and sleep-promoting properties in rats
Brotschi, C., Bolli, M. H., Gatfield, J., Roch, C., Sifferlen, T., Treiber, A., Williams, J. T., & Boss, C. (2023) · RSC Medicinal Chemistry · doi:10.1039/d3md00573a · Cited by 4
Biphasic feature of placebo response in primary insomnia: pooled analysis of data from randomized controlled clinical trials of orexin receptor antagonists
He, D., Jiang, B., Guo, Z., Mu, Q., & McClure, M. A. (2019) · SLEEP · doi:10.1093/sleep/zsz238 · Cited by 3
The "anatomizing" of criminals.
Dobson, J. F. (1951) · PubMed Central · Cited by 3
Sleep disturbances in traumatic exposure and post-traumatic stress disorder
El-Solh, A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822963-7.00075-x · Cited by 3
Circadian Rhythm in Respiratory Medicine
González, A. A. (2022) · Clinical Research and Trials · doi:10.15761/crt.1000367 · Cited by 2
The effect of the initial administration of suvorexant on severe sleep apnea syndrome
Mieno, Y., Hayashi, M., Souma, T., Horiguchi, T., Niwa, Y., Fujita, S., Fukumoto, J., Hosoda, N., & Imaizumi, K. (2024) · Sleep and Biological Rhythms · doi:10.1007/s41105-024-00548-7 · Cited by 2

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
ORCID: Coleman, Paul J.
Gotter, Anthony L.
Herring, W. Joseph
Winrow, Christopher J.
Renger, John J.
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
DOI: 10.1146/annurev-pharmtox-010716-104837
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

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

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks