ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2013
Quantitative electroencephalography within sleep/wake states differentiates GABAA modulators eszopiclone and zolpidem from dual orexin receptor antagonists in rats.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Distinct effects of orexin receptor antagonist and GABAProceedings of the National Academy of Sciences of the United States of America · 2019Trial
- Orexin 2 Receptor Antagonism is Sufficient to Promote NREM and REM Sleep from Mouse to Man.Scientific reports · 2016Trial
- Trial
- Wake-promoting neuromodulators in Alzheimer's disease: Implications for sleep and brain clearance.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Ethanol-induced rapid eye movement sleep suppression in rats: Comparison with subtype-selective GABAJournal of psychopharmacology (Oxford, England) · 2025Article
- Emerging and upcoming therapies in insomnia.Translational and clinical pharmacology · 2024Article
- Differential sleep/wake response and sex differences following acute suvorexant, MK-1064 and zolpidem administration in the rTg4510 mouse model of tauopathy.British journal of pharmacology · 2022Article
- Nonclinical pharmacology of daridorexant: a new dual orexin receptor antagonist for the treatment of insomnia.Psychopharmacology · 2021Review
- Eszopiclone and Zolpidem Produce Opposite Effects on Hippocampal Ripple Density.Frontiers in pharmacology · 2021Article
- Hypnotics with novel modes of action.British journal of clinical pharmacology · 2020Review
- Neurophysiological and Behavioral Effects of Anti-Orexinergic Treatments in a Mouse Model of Huntington's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Article
- Article
- Inhibition of Orexin Signaling Promotes Sleep Yet Preserves Salient Arousability in Monkeys.Sleep · 2016Article
- State-dependent alterations in sleep/wake architecture elicited by the M4 PAM VU0467154 - Relation to antipsychotic-like drug effects.Neuropharmacology · 2016Article
- Differential sleep-promoting effects of dual orexin receptor antagonists and GABAA receptor modulators.BMC neuroscience · 2014Article
- Orexin receptor antagonist-induced sleep does not impair the ability to wake in response to emotionally salient acoustic stimuli in dogs.Frontiers in behavioral neuroscience · 2014Article
- Enhanced slow-wave EEG activity and thermoregulatory impairment following the inhibition of the lateral hypothalamus in the rat.PloS one · 2014Article
- The duration of sleep promoting efficacy by dual orexin receptor antagonists is dependent upon receptor occupancy threshold.BMC neuroscience · 2013Article
- Dual orexin receptor antagonists show distinct effects on locomotor performance, ethanol interaction and sleep architecture relative to gamma-aminobutyric acid-A receptor modulators.Frontiers in neuroscience · 2013Article
- Kinetic properties of "dual" orexin receptor antagonists at OX1R and OX2R orexin receptors.Frontiers in neuroscience · 2013Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dual orexin receptor antagonists (DORAs) induce sleep by blocking orexin 1 and orexin 2 receptor-mediated activities responsible for regulating wakefulness. DORAs represent a potential alternative mechanism to the current standard of care that includes the γ-aminobutyric acid (GABA)A receptor-positive allosteric modulators, eszopiclone and zolpidem. This work uses an innovative method to analyze electroencephalogram (EEG) spectral frequencies within sleep/wake states to differentiate the effects of GABAA modulators from DORA-22, an analog of the DORA MK-6096, in Sprague-Dawley rats. The effects of low, intermediate, and high doses of eszopiclone, zolpidem, and DORA-22 were examined after first defining each compound's ability to promote sleep during active-phase dosing. The EEG spectral frequency power within specific sleep stages was calculated in 1-Hz intervals from 1 to 100 Hz within each sleep/wake state for the first 4 h after the dose. Eszopiclone and zolpidem produced marked, dose-responsive disruptions in sleep stage-specific EEG spectral profiles compared with vehicle treatment. In marked contrast, DORA-22 exhibited marginal changes in the spectral profile, observed only during rapid eye movement sleep, and only at the highest dose tested. Moreover, while eszopiclone- and zolpidem-induced changes were evident in the inactive period, the EEG spectral responses to DORA-22 were absent during this phase. These results suggest that DORA-22 differs from eszopiclone and zolpidem whereby DORA-22 promotes somnolence without altering the neuronal network EEG activity observed during normal sleep.
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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.