The orexin system consists of two G-protein-coupled receptors, the orexin 1 and orexin 2 receptors, widely expressed in diverse regions of the brain, and two peptide agonists, orexin A and orexin B, which are produced in a small assembly of neurons in the lateral hypothalamus. The orexin system plays an important role in the maintenance of wakefulness. Several compounds (almorexant, SB-649868, suvorexant) have been in advanced clinical trials for treating primary insomnia. ACT-462206 is a new, potent, and selective dual orexin receptor antagonist (DORA) that inhibits the stimulating effects of the orexin peptides at both the orexin 1 and 2 receptors. It decreases wakefulness and increases non-rapid eye movement (non-REM) and REM sleep while maintaining natural sleep architectures in rat and dog electroencephalography/electromyography (EEG/EMG) experiments. ACT-462206 shows anxiolytic-like properties in rats without affecting cognition and motor function. It is therefore a potential candidate for the treatment of insomnia.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/cmdc.201402258 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The interaction between orexin, sleep deprivation and Alzheimer's disease: Unveiling an Emerging Connection.
J Physiol Sci
January 2025
Department of Neuroscience, School of Science and Advanced Technologies in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive decline and memory loss. Sleep-wake disorders are an extremely predominant and often disabling aspect of AD. Ox is vital in maintaining the sleep-wake cycle and promoting wakefulness.
View Article and Find Full Text PDFEffect of Lemborexant on Daytime Functioning in Adults With Insomnia: Patient-Reported Outcomes From a Phase 3 Clinical Trial.
Prim Care Companion CNS Disord
January 2025
Eisai Inc, Nutley, New Jersey.
Insomnia and some insomnia treatments can impact an individual's daytime functioning. Here, we performed post hoc analyses of patient-reported outcomes from a phase 3 clinical trial to assess the impact of lemborexant (LEM), a dual orexin receptor antagonist, on daytime functioning. Adults with insomnia were randomized 1:1:1 to receive placebo, LEM 5 mg (LEM5) or LEM 10 mg (LEM10) for 6 months.
View Article and Find Full Text PDFCan serum orexin levels be used as a marker in childhood epilepsy?
Heliyon
January 2025
Department of Pediatric Neurology, University of Health Sciences, Gülhane Training and Research Hospital, Ankara, the Republic of Türkiye.
Objective: Epilepsy is one of the most common neurological diseases in the pediatric population. Orexins are excitatory peptides and associated with energy homeostasis, eating and drinking behaviors, sleep regulation, sleep-wake periods, analgesia, and cognitive activities such as attention, learning, and memory. The aim of this study was to reveal the relationship between plasma orexin levels and seizures in pediatric epilepsy patients with seizures, epilepsy patients in remission, and healthy control group with similar demographic characteristics.
View Article and Find Full Text PDFPhase 1b/2a safety study of lemborexant as an adjunctive treatment for insomnia to buprenorphine-naloxone for opioid use disorder: A randomized controlled trial.
Drug Alcohol Depend Rep
March 2025
Institute for Drug and Alcohol Studies, Virginia Commonwealth University, 203 East Cary Street, Richmond, VA 23219, USA.
Background: Evidence supports the common incidence of sleep disturbance in opioid use disorder (OUD) as a potential marker of disrupted orexin system functioning. This study evaluated the initial safety and tolerability of a challenge dose of lemborexant, a dual orexin antagonist, as an adjunct to buprenorphine/naloxone.
Methods: Patients (18-65 years old) with OUD receiving sublingual buprenorphine/naloxone, with a Pittsburgh Sleep Quality Index total score of 6 or higher, were recruited from outpatient clinics.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!