ArticleProceedings of the National Academy of Sciences of the United States of America2022
Orexin 2 receptor-selective agonist danavorexton improves narcolepsy phenotype in a mouse model and in human patients.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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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.
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Who cites it
32 citing papers in PubMed, 87 citations in OpenAlex.
- Trial
- Safety and pharmacodynamics of a single infusion of danavorexton in adults with idiopathic hypersomnia.Sleep · 2023Trial
- Suvorexant Acutely Decreases Tau Phosphorylation and Aβ in the Human CNS.Annals of neurology · 2023Trial
- Therapeutic potential of targeting the orexin (hypocretin) system in sleep disorders.Nature reviews. Endocrinology · 2026Review
- Effects of Vornorexant, a Dual Orexin Receptor Antagonist, on Bladder Function in Rats and Nocturnal Voiding Frequency in Patients With Insomnia.International journal of urology : official journal of the Japanese Urological Association · 2026Article
- Effects of an orexin receptor 2-selective agonist on salivary secretion in rats.Scientific reports · 2026Article
- Narcolepsy as an immune-associated hypothalamic encephalopathy: orexin dysfunction and implications for precision sleep medicine.Frontiers in psychiatry · 2026Review
- Lost in translation-what is translational neuroscience research?Brain communications · 2026Article
- The Role of Danavorexton for Perioperative Opioid-Induced Respiratory Depression and Sedation: A Narrative Review.Clinical pharmacology : advances and applications · 2026Review
- Recent Advances and Emerging Pharmacotherapeutic Approaches for Central Hypersomnolence Disorders.Clinical pharmacology : advances and applications · 2026Review
- Orexin receptor 2 agonists: a pathophysiologic approach to narcolepsy type 1.Annals of medicine and surgery (2012) · 2026Article
- Awakening Recovery: Enhancing Orexinergic Tone After Acute CNS Damage.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Longitudinal Associations of Serum Orexin-A With Physical Activity and Sleep in Schizophrenia: A Preliminary Study.Neuropsychopharmacology reports · 2025Article
- A Comprehensive Review of Current and Emerging Treatments for Narcolepsy Type 1.Journal of clinical medicine · 2025Review
- Hypothalamic functional connectivity, depressive symptoms, and post-treatment SOREMPs in narcolepsy type 1: links to sleep latency and mediation mechanisms.Translational psychiatry · 2025Article
- Animal Models of Narcolepsy: From Orexin Deficiency to Immune Mechanisms and Regenerative Therapies.Current issues in molecular biology · 2025Review
- Present and Future of Central Disorders of Hypersomnolence.Journal of sleep research · 2025Review
- Sleep as the Foundation of Brain Health.Seminars in neurology · 2025Review
- Alluring Potential to Accelerate Emergence and Ameliorate Opioid-induced Respiratory Depression without Antagonizing Analgesia: Danavorexton Enters the Anesthetic Landscape.Anesthesiology · 2025Article
- Narcolepsy and rapid eye movement sleep.Journal of sleep research · 2025Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Narcolepsy type 1 (NT1) is a sleep disorder caused by a loss of orexinergic neurons. Narcolepsy type 2 (NT2) is heterogeneous; affected individuals typically have normal orexin levels. Following evaluation in mice, the effects of the orexin 2 receptor (OX2R)-selective agonist danavorexton were evaluated in single- and multiple-rising-dose studies in healthy adults, and in individuals with NT1 and NT2. In orexin/ataxin-3 narcolepsy mice, danavorexton reduced sleep/wakefulness fragmentation and cataplexy-like episodes during the active phase. In humans, danavorexton administered intravenously was well tolerated and was associated with marked improvements in sleep latency in both NT1 and NT2. In individuals with NT1, danavorexton dose-dependently increased sleep latency in the Maintenance of Wakefulness Test, up to the ceiling effect of 40 min, in both the single- and multiple-rising-dose studies. These findings indicate that OX2Rs remain functional despite long-term orexin loss in NT1. OX2R-selective agonists are a promising treatment for both NT1 and NT2.
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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.