ArticleSleep2016
Inhibition of Orexin Signaling Promotes Sleep Yet Preserves Salient Arousability in Monkeys.
Article in Sleep, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03312517 (A Phase IV 3-Way Double-blind, Randomized, Crossover Study to Compare the Awakening Threshold Effects), which is not on this map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase IV 3-Way Double-blind, Randomized, Crossover Study to Compare the Awakening Threshold Effects (Responsivity) of Belsomra 10 mg and 20 mg to Placebo in Non-elderly Insomniacs
Who cites it
25 citing papers in PubMed, 46 citations in OpenAlex.
- Pharmacokinetics, safety, and efficacy of daridorexant in Japanese subjects: Results from phase 1 and 2 studies.Journal of sleep research · 2025Trial
- Trial
- Trial
- Distinct effects of orexin receptor antagonist and GABAProceedings of the National Academy of Sciences of the United States of America · 2019Trial
- Can the Orexin Antagonist Suvorexant Preserve the Ability to Awaken to Auditory Stimuli While Improving Sleep?Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2019Trial
- The sleep-wake cycle: molecular mechanisms, disorders, and therapeutic targets in the context of energy metabolism.Signal transduction and targeted therapy · 2026Review
- Daridorexant and Insomnia in Clinical Practice: A Nominal Group Technique Consensus Study among Italian Sleep and Insomnia Experts.Current neuropharmacology · 2026Article
- Slow wave electroencephalogram spectral properties during adaptation of a new light dark cycle in cynomolgus monkeys.Sleep advances : a journal of the Sleep Research Society · 2026Article
- A new direction for adjunctive therapy of difficult-to-treat depression: examining the role of orexin receptor antagonists.European archives of psychiatry and clinical neuroscience · 2025Review
- Effects of methamphetamine on actigraphy-based sleep parameters in female rhesus monkeys: Orexin receptor mechanisms.Drug and alcohol dependence · 2024Article
- Readjustment of circadian clocks by exercise intervention is a potential therapeutic target for sleep disorders: a narrative review.Physical activity and nutrition · 2024Article
- Emerging and upcoming therapies in insomnia.Translational and clinical pharmacology · 2024Article
- Increased Risk of Sudden Sensorineural Hearing Loss in Patients Receiving Sedative-Hypnotics: A Propensity Score Weighting Cohort Study.Nature and science of sleep · 2024Article
- Treatment of sleep-related eating disorder with suvorexant: A case report on the potential benefits of replacing benzodiazepines with orexin receptor antagonists.PCN reports : psychiatry and clinical neurosciences · 2023Article
- Nonclinical pharmacology of daridorexant: a new dual orexin receptor antagonist for the treatment of insomnia.Psychopharmacology · 2021Review
- Alprazolam-induced EEG spectral power changes in rhesus monkeys: a translational model for the evaluation of the behavioral effects of benzodiazepines.Psychopharmacology · 2021Article
- Circadian rhythm as a therapeutic target.Nature reviews. Drug discovery · 2021Review
- Suvorexant improves intractable nocturnal enuresis by altering sleep architecture.BMJ case reports · 2021Article
- Trace amine-associated receptor 1 agonism promotes wakefulness without impairment of cognition in Cynomolgus macaques.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
- Hypocretin Mediates Sleep and Wake Disturbances in a Mouse Model of Traumatic Brain Injury.Journal of neurotrauma · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
STUDY
objectivesIn addition to enhancing sleep onset and maintenance, a desirable insomnia therapeutic agent would preserve healthy sleep's ability to wake and respond to salient situations while maintaining sleep during irrelevant noise. Dual orexin receptor antagonists (DORAs) promote sleep by selectively inhibiting wake-promoting neuropeptide signaling, unlike global inhibition of central nervous system excitation by gamma-aminobutyric acid (GABA)-A receptor (GABAaR) modulators. We evaluated the effect of DORA versus GABAaR modulators on underlying sleep architecture, ability to waken to emotionally relevant stimuli versus neutral auditory cues, and performance on a sleepiness-sensitive cognitive task upon awakening.
methodsDORA-22 and GABAaR modulators (eszopiclone, diazepam) were evaluated in adult male rhesus monkeys (n = 34) with continuous polysomnography recordings in crossover studies of sleep architecture, arousability to a classically conditioned salient versus neutral acoustical stimulus, and psychomotor vigilance task (PVT) performance if awakened.
resultsAll compounds decreased wakefulness, but only DORA-22 sleep resembled unmedicated sleep in terms of underlying sleep architecture, preserved ability to awaken to salient-conditioned acoustic stimuli while maintaining sleep during neutral acoustic stimuli, and no congnitive impairment in PVT performance. Although GABAaR modulators induced lighter sleep, monkeys rarely woke to salient stimuli and PVT performance was impaired if monkeys were awakened.
conclusionsIn nonhuman primates, DORAs' targeted mechanism for promoting sleep protects the ability to selectively arouse to salient stimuli and perform attentional tasks unimpaired, suggesting meaningful differentiation between a hypnotic agent that works through antagonizing orexin wake signaling versus the sedative hypnotic effects of the GABAaR modulator mechanism of action.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.