Orexants, Orexin Receptor Antagonists: Novel Therapeutic Agents for Insomnia Disorder
Akshitha Kandukuri, Haritha Pasupulati, Satyanarayana SV Padi
International Neuropsychiatric Disease Journal · pp. 92–108 · Published 2 Dec 2024
10.9734/indj/2024/v21i6457Abstract
Insomnia is when a person feels difficulty falling asleep or staying asleep, often associated with complications, such as fatigue, sleepiness, etc. Insomnia may cause disruptions in daytime physical and mental abilities. Orexins or hypocretins are the neuropeptides secreted from the lateral hypothalamus and play a major role in the sleep-wake cycle through a complex interplay between wake-promoting and sleep-promoting neuronal systems. Orexin receptor antagonists (Orexants) are the new treatment options for insomnia disorder, narcolepsy, and other sleep disturbances. There are two classes of Orexants, namely those that bind selectively to a specific orexin receptor are selective orexin receptor antagonists (SORA), and the others that bind to both the orexin receptors are dual orexin receptor antagonists (DORA). The first DORA was almorexant but restricted in use and the other three approved DORAs, such as suvorexant, lemborexant, and daridorexant were approved by the FDA, and several other DORAs and SORAs are under various stages of discovery and clinical investigation. Among the labeled limitations, the currently approved Orexants are contraindicated in people with narcolepsy and are controlled substances owing to their misuse liability. The present review discussed the sleep-wake cycle, phases of a sleep cycle, orexins, and Orexants, and summarized the pharmacology of the three approved DORAs, a type of Orexants and their potential advantages and limitations of their use in pharmacotherapy of insomnia disorder.
References (66)
- 1 American Geriatrics Society 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults [DOI]
- 2 Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline [DOI]
- 3 Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis [DOI]
- 4 Lemborexant, A Dual Orexin Receptor Antagonist (DORA) for the Treatment of Insomnia Disorder: Results From a Bayesian, Adaptive, Randomized, Double-Blind, Placebo-Controlled Study [DOI]
- 5 Neuro-orchestration of sleep and wakefulness [DOI]
- 6 Discovery and development of orexin receptor antagonists as therapeutics for insomnia [DOI]
- 7 Automated Detection of Sleep Stages Using Deep Learning Techniques: A Systematic Review of the Last Decade (2010–2020) [DOI]
- 8 Orexin Receptor Antagonists as Emerging Treatments for Psychiatric Disorders [DOI]
- 9 The orexin story and orexin receptor antagonists for the treatment of insomnia [DOI]
- 10 Non-pharmacological Approaches for Management of Insomnia [DOI]
- 11 Long-Term Safety and Tolerability of Daridorexant in Patients with Insomnia Disorder [DOI]
- 12 Daridorexant, a new dual orexin receptor antagonist, in elderly subjects with insomnia disorder [DOI]
- 13 Clinical pharmacology, efficacy, and safety of orexin receptor antagonists for the treatment of insomnia disorders [DOI]
- 14 An Update on Dual Orexin Receptor Antagonists and Their Potential Role in Insomnia Therapeutics [DOI]
- 15 Lemborexant: First Approval [DOI]
- 16 Daridorexant: First Approval [DOI]
- 17 A systematic analysis of ICSD-3 diagnostic criteria and proposal for further structured iteration [DOI]
- 18 Brain stimulation techniques as novel treatment options for insomnia: A systematic review [DOI]
- 19 Targeting Orexin Receptors for the Treatment of Insomnia: From Physiological Mechanisms to Current Clinical Evidence and Recommendations [DOI]
- 20 The safety and efficacy of gabapentinoids in the management of neuropathic pain: a systematic review with meta-analysis of randomised controlled trials [DOI]
- 21 Efficacy and Safety of Daridorexant in Older and Younger Adults with Insomnia Disorder: A Secondary Analysis of a Randomised Placebo-Controlled Trial [DOI]
- 22 Insomnia Management: A Review and Update [DOI]
- 23 Lack of residual morning effects of lemborexant treatment for insomnia: summary of findings across 9 clinical trials [DOI]
- 24 Sleep-Wake Neurochemistry [DOI]
- 25 A 2023 Update on Managing Insomnia in Primary Care [DOI]
- 26 Use of Melatonin and/on Ramelteon for the Treatment of Insomnia in Older Adults: A Systematic Review and Meta-Analysis [DOI]
- 27 Dual orexin receptor antagonists for treatment of insomnia: A systematic review and meta-analysis on randomized, double-blind, placebo-controlled trials of suvorexant and lemborexant [DOI]
- 28 Efficacy of melatonin and ramelteon for the acute and long‐term management of insomnia disorder in adults: A systematic review and meta‐analysis [DOI]
- 29 Effect of discontinuation of lemborexant following long‐term treatment of insomnia disorder: Secondary analysis of a randomized clinical trial [DOI]
- 30 Adverse effects of antipsychotics on sleep in patients with schizophrenia. Systematic review and meta-analysis [DOI]
- 31 Complementary and alternative treatments for insomnia disorder: a systematic umbrella review [DOI]
- 32 Different doses of dual orexin receptor antagonists in primary insomnia: a Bayesian network analysis [DOI]
- 33 Acute and Chronic Insomnia: What Has Time and/or Hyperarousal Got to Do with It? [DOI]
- 34 Respiratory safety of lemborexant in healthy adult and elderly subjects with mild obstructive sleep apnea: A randomized, double‐blind, placebo‐controlled, crossover study [DOI]
- 35 Effect of the new dual orexin receptor antagonist daridorexant on nighttime respiratory function and sleep in patients with mild and moderate obstructive sleep apnea [DOI]
- 36 Updates in insomnia diagnosis and treatment [DOI]
- 37 Discovery of ORN0829, a potent dual orexin 1/2 receptor antagonist for the treatment of insomnia [DOI]
- 38 Effects of TS-142, a novel dual orexin receptor antagonist, on sleep in patients with insomnia: a randomized, double-blind, placebo-controlled phase 2 study [DOI]
- 39 Suvorexant, a Novel Dual Orexin Receptor Antagonist, for the Management of Insomnia [DOI]
- 40 Assessment of the effect of the dual orexin receptor antagonist daridorexant on various indices of disease severity in patients with mild to moderate obstructive sleep apnea [DOI]
- 41 Daridorexant for the Treatment of Insomnia [DOI]
- 42 Efficacy, safety, and tolerability of nivasorexant in adults with binge‐eating disorder: A randomized, Phase II proof of concept trial [DOI]
- 43 Daridorexant in Insomnia Disorder: A Profile of Its Use [DOI]
- 44 Pharmacological and non-pharmacological treatments for insomnia [DOI]
- 45 The neurophysiologic basis of the human sleep–wake cycle and the physiopathology of the circadian clock: a narrative review [DOI]
- 46 Evaluating lemborexant for the treatment of insomnia [DOI]
- 47 Experimental Drugs for Panic Disorder: An Updated Systematic Review [DOI]
- 48 Suvorexant in the Treatment of Difficulty Falling and Staying Asleep (Insomnia) [DOI]
- 49 Lemborexant (Dayvigo) for the Treatment of Insomnia.
- 50 The Discovery of Suvorexant: Lessons Learned That Can Be Applied to Other CNS Drug Development Efforts [DOI]
- 51 The European Insomnia Guideline: An update on the diagnosis and treatment of insomnia 2023 [DOI]
- 52 Orexin Receptor Antagonism: Normalizing Sleep Architecture in Old Age and Disease [DOI]
- 53 Insomnia in neurological disorders: Prevalence, mechanisms, impact and treatment approaches [DOI]
- 54 Clinical usefulness of dual orexin receptor antagonism beyond insomnia: Neurological and psychiatric comorbidities [DOI]
- 55 Orexin receptor antagonists in the treatment of insomnia associated with psychiatric disorders: a systematic review [DOI]
- 56 Orexinergic Receptor Antagonists as a New Therapeutic Target to Overcome Limitations of Current Pharmacological Treatment of Insomnia Disorder [DOI]
- 57 Emerging and upcoming therapies in insomnia [DOI]
- 58 Molecular Docking and Dynamics Studies of Withania somnifera Derived Compounds as GABA-A Receptor Modulators for Insomnia [DOI]
- 59 Improving Sleep Quality, Daytime Sleepiness, and Cognitive Function in Patients with Dementia by Therapeutic Exercise and NESA Neuromodulation: A Multicenter Clinical Trial [DOI]
- 60 Efficacy and safety of insomnia treatment with lemborexant in older adults: analyses from three clinical trials [DOI]
- 61 Insomnia: A Current Review.
- 62 Safety and Efficacy of Lemborexant in Insomnia Patients: Results of a Postmarketing Observational Study of Dayvigo® Tablets [DOI]
- 63 Effect of nivasorexant ( ACT ‐539313), a selective orexin‐1‐receptor antagonist, on multiple cytochrome P450 probe substrates in vitro and in vivo using a cocktail approach in healthy subjects [DOI]
- 64 Assessment and management of chronic insomnia disorder: an algorithm for primary care physicians [DOI]
- 65 Pharmacological Treatments of Sleep–Wake Disorders: Update 2023 [DOI]
- 66 Overview of Adverse Drug Reactions: Classification, Reporting, Prevention, and Role of Pharmacist [DOI]
Cited by 2
2 citations reported by external sources — individual citing-article records aren't available to list yet.
Related research
- Psychological Wellbeing of Healthcare Workers in Different Hospitals of Karachi (Pakistan) During COVID-19 Pandemic — shares topic coverage
- Association of Poor Sleep Quality with Ischemic Heart Disease — shares topic coverage
- Research Findings for Sleep Disorders: A Literature Update — shares topic coverage
- Sleep Patterns Across Different Age Groups: A Survey Study in Ballari City, Karnataka, India — shares topic coverage
- Effect of Aerobic Exercise on Depression and Insomnia in Post Menopausal Women — shares topic coverage
Article metrics
Real usage data collected on this platform.
38
Page views
0
PDF downloads
13
Outbound clicks
2
Citations
Views over time
Views by country
Approximate, from request IP at view time — not citizenship or institution. Countries with fewer than 5 views are grouped as "Other".
Traffic sources
Referring site, by host.
Views and downloads exclude known bots/crawlers. Citations combines this platform's own DOI-resolved index with each external source's own reported total — see Cited by above for individually listed citing works. Last refreshed 0 seconds ago.