ArticleFrontiers in behavioral neuroscience2014
Orexin receptor antagonist-induced sleep does not impair the ability to wake in response to emotionally salient acoustic stimuli in dogs.
Article in Frontiers in behavioral neuroscience, 2014. 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 17 papers.
What it found
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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
17 citing papers in PubMed, 37 citations in OpenAlex.
- Pharmacokinetics, safety, and efficacy of daridorexant in Japanese subjects: Results from phase 1 and 2 studies.Journal of sleep research · 2025Trial
- 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
- Orexin 2 Receptor Antagonism is Sufficient to Promote NREM and REM Sleep from Mouse to Man.Scientific reports · 2016Trial
- Activity of putative orexin neurons during cataplexy.Molecular brain · 2022Article
- Article
- Nonclinical pharmacology of daridorexant: a new dual orexin receptor antagonist for the treatment of insomnia.Psychopharmacology · 2021Review
- Article
- The Discovery of Suvorexant: Lessons Learned That Can Be Applied to Other CNS Drug Development Efforts.ACS pharmacology & translational science · 2020Article
- Hypnotics with novel modes of action.British journal of clinical pharmacology · 2020Review
- Orexin Receptor Blockade-Induced Sleep Preserves the Ability to Wake in the Presence of Threat in Mice.Frontiers in behavioral neuroscience · 2018Article
- Pharmacological validation of a novel nonhuman primate measure of thermal responsivity with utility for predicting analgesic effects.Journal of pain research · 2018Article
- Orexin 2 receptor regulation of the hypothalamic-pituitary-adrenal (HPA) response to acute and repeated stress.Neuroscience · 2017Article
- Inhibition of Orexin Signaling Promotes Sleep Yet Preserves Salient Arousability in Monkeys.Sleep · 2016Article
- The Dual Hypocretin Receptor Antagonist Almorexant is Permissive for Activation of Wake-Promoting Systems.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- Differential sleep-promoting effects of dual orexin receptor antagonists and GABAA receptor modulators.BMC neuroscience · 2014Article
- Orexin OXCurrent topics in behavioral neurosciencesReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ability to awaken from sleep in response to important stimuli is a critical feature of normal sleep, as is maintaining sleep continuity in the presence of irrelevant background noise. Dual orexin receptor antagonists (DORAs) effectively promote sleep across species by targeting the evolutionarily conserved wake-promoting orexin signaling pathway. This study in dogs investigated whether DORA-induced sleep preserved the ability to awaken appropriately to salient acoustic stimuli but remain asleep when exposed to irrelevant stimuli. Sleep and wake in response to DORAs, vehicle, GABA-A receptor modulators (diazepam, eszopiclone and zolpidem) and antihistamine (diphenhydramine) administration were evaluated in telemetry-implanted adult dogs with continuous electrocorticogram, electromyogram (EMG), electrooculogram (EOG), and activity recordings. DORAs induced sleep, but GABA-A modulators and antihistamine induced paradoxical hyperarousal. Thus, salience gating studies were conducted during DORA-22 (0.3, 1, and 5 mg/kg; day and night) and vehicle nighttime sleep. The acoustic stimuli were either classically conditioned using food reward and positive attention (salient stimulus) or presented randomly (neutral stimulus). Once conditioned, the tones were presented at sleep times corresponding to maximal DORA-22 exposure. In response to the salient stimuli, dogs woke completely from vehicle and orexin-antagonized sleep across all sleep stages but rarely awoke to neutral stimuli. Notably, acute pharmacological antagonism of orexin receptors paired with emotionally salient anticipation produced wake, not cataplexy, in a species where genetic (chronic) loss of orexin receptor signaling leads to narcolepsy/cataplexy. DORA-induced sleep in the dog thereby retains the desired capacity to awaken to emotionally salient acoustic stimuli while preserving uninterrupted sleep in response to irrelevant stimuli.
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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.