ArticleSleep2012
The dual orexin receptor antagonist almorexant induces sleep and decreases orexin-induced locomotion by blocking orexin 2 receptors.
Article in Sleep, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 99 citations in OpenAlex.
- First-in-human study with ACT-539313, a novel selective orexin-1 receptor antagonist.British journal of clinical pharmacology · 2020Trial
- Orexin 2 Receptor Antagonism is Sufficient to Promote NREM and REM Sleep from Mouse to Man.Scientific reports · 2016Trial
- Temporal profile of serum orexin-A in neonatal hypoxic-ischemic encephalopathy: a prospective longitudinal study.BMC pediatrics · 2026Observational
- Effects of daridorexant on sleep architecture in Japanese patients with insomnia disorder: analysis of a phase II randomized controlled trial.Sleep and biological rhythms · 2026Article
- Estimation of the Orexin Receptor Occupancy From Human Plasma Pharmacokinetics of Vornorexant, a Novel Dual Orexin 1/2 Receptor Antagonist for the Treatment of Insomnia.Pharmacology research & perspectives · 2026Article
- Efficacy and Safety Profile of Suvorexant for the Treatment of Insomnia.Current drug safety · 2026Review
- Daily treatment with the dual orexin receptor antagonist DORA-12 during oxycodone abstinence decreases oxycodone conditioned reinstatement.Neuropharmacology · 2023Article
- Article
- Development of NovelACS medicinal chemistry letters · 2023Article
- 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
- Orexin Signaling: A Complex, Multifaceted Process.Frontiers in cellular neuroscience · 2022Review
- Exploring the Role of Orexinergic Neurons in Parkinson's Disease.Neurotoxicity research · 2021Review
- At the intersection of sleep deficiency and opioid use: mechanisms and therapeutic opportunities.Translational research : the journal of laboratory and clinical medicine · 2021Review
- Inhibition of Orexin/Hypocretin Neurons Ameliorates Elevated Physical Activity and Energy Expenditure in the A53T Mouse Model of Parkinson's Disease.International journal of molecular sciences · 2021Article
- Article
- Article
- Pharmacological characterization of a novel potent, selective, and orally active orexin 2 receptor antagonist, SDM-878.Neuropsychopharmacology reports · 2020Article
- Orexin Receptor Antagonists as Emerging Treatments for Psychiatric Disorders.Neuroscience bulletin · 2020Review
- Hypnotics with novel modes of action.British journal of clinical pharmacology · 2020Review
- Chemogenetic activation of orexin/hypocretin neurons ameliorates aging-induced changes in behavior and energy expenditure.American journal of physiology. Regulatory, integrative and comparative physiology · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
STUDY
objectivesOrexin peptides activate orexin 1 and orexin 2 receptors (OX(1)R and OX(2)R), regulate locomotion and sleep-wake. The dual OX(1)R/OX(2)R antagonist almorexant reduces activity and promotes sleep in multiple species, including man. The relative contributions of the two receptors in locomotion and sleep/wake regulation were investigated in mice.
designMice lacking orexin receptors were used to determine the contribution of OX(1)R and OX(2)R to orexin A-induced locomotion and to almorexant-induced sleep.
settingN/A. PATIENTS OR
participantsC57BL/6J mice and OX(1)R(+/+), OX(1)R(-/-), OX(2)R(+/+), OX(2)R(-/-) and OX(1)R(-/-)/OX(2)R(-/-) mice.
interventionsIntracerebroventricular orexin A; oral dosing of almorexant. MEASUREMENTS AND
resultsAlmorexant attenuated orexin A-induced locomotion. As in other species, almorexant dose-dependently increased rapid eye movement sleep (REM) and nonREM sleep in mice. Almorexant and orexin A were ineffective in OX(1)R(-/-)/OX(2)R(-/-) mice. Both orexin A-induced locomotion and sleep induction by almorexant were absent in OX(2)R(-/-) mice. Interestingly, almorexant did not induce cataplexy in wild-type mice under conditions where cataplexy was seen in mice lacking orexins and in OX(1)R(-/-)/OX(2)R(-/-) mice. Almorexant dissociates very slowly from OX(2)R as measured functionally and in radioligand binding. Under non equilibrium conditions in vitro, almorexant was a dual antagonist whereas at equilibrium, almorexant became OX(2)R selective.
conclusionsIn vivo, almorexant specifically inhibits the actions of orexin A. The two known orexin receptors mediate sleep induction by almorexant and orexin A-induced locomotion. However, OX(2)R activation mediates locomotion induction by orexin A and antagonism of OX(2)R is sufficient to promote sleep in mice.
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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.