Effects of orexin receptor antagonism on human sleep architecture: A systematic review.

@article{Clark2020EffectsOO,
  title={Effects of orexin receptor antagonism on human sleep architecture: A systematic review.},
  author={Jacob W Clark and Maddison L. Brian and Sean P. A. Drummond and Daniel Hoyer and Laura H. Jacobson},
  journal={Sleep medicine reviews},
  year={2020},
  volume={53},
  pages={
          101332
        }
}

Dual orexin receptor antagonists for insomnia in youth with neurodevelopmental disorders: a case series and review

Four patients with NDDs and insomnia that are treated with the DORA, suvorexant, found that patients had a wide range of responses, with one patient displaying a robust improvement in sleep onset and maintenance, while another had significant improvement in insomnia symptoms on combination therapy with trazodone.

Novel 5-Alkyl Pyrrolidine Orexin Receptor Agonists for Treating Sleep Disorders.

  • R. W. Sabnis
  • Chemistry, Biology
    ACS medicinal chemistry letters
  • 2020
The present application describes a series of novel 5-alkyl pyrrolidine compounds as orexin receptor agonists for the treatment or prevention of neurological and psychiatric disorders and diseases, particularly sleep disorders.

Hypocretins (orexins): The ultimate translational neuropeptides

Circuit neuroscience findings suggest that the Hcrt system is a hub that integrates diverse inputs modulating arousal and conveys this information to multiple output regions and highlights the potential of the HCrt system as a therapeutic target for a number of disorders.

Sleep Problems in Narcolepsy and the Role of Hypocretin/Orexin Deficiency.

Current analyses suggest that the main functions of the hypocretin/orexin system are maintenance of wakefulness in the face of moderate sleep deprivation and inhibition of REM sleep, with possible differential modulating effects on various subcomponents of the sleep-stage, explaining REM sleep dissociation events in NT1.

Hypocretin/Orexin Receptor Pharmacology and Sleep Phases.

The broad projections of the hypocretin/orexin-producing neurons, along with differential expression of the two receptors in the projection fields of these neurons, suggest distinct roles for these receptors.

Causes and Consequences of Chronic Sleep Deficiency and the Role of Orexin.

Dual and selective orexin-2 receptor antagonists have shown efficacy in inducing sleep in men and women with insomnia disorder by accelerating sleep onset and improving sleep efficiency and total sleep time.

Suvorexant ameliorated sleep disturbance, opioid withdrawal, and craving during a buprenorphine taper

Suvorexant reduced sleep disturbance during opioid withdrawal and may improve opioid use disorder treatment outcomes, and targeting the orexin signaling might reduce the negative effects of opioid withdrawal on sleep quality.

Manipulation of REM sleep via orexin and GABAA receptor modulators differentially affects fear extinction in mice: effect of stable versus disrupted circadian rhythm.

Preclinical evidence is provided for the potential clinical utility of hypnotics which increase REM sleep for fear extinction after PTSD-relevant sleep disturbance and suvorexant increased REM sleep and improved fear extinction rate, relative to zolpidem, which decreased REM sleep.

Advances in the Treatment of Chronic Insomnia: A Narrative Review of New Nonpharmacologic and Pharmacologic Therapies

A narrative review provides a summary of the diagnostic criteria and pathophysiology of insomnia and its subtypes and emphasizes new and emerging nonpharmacologic and pharmacologic treatments for chronic insomnia, including recent enhancements in approaches to cognitive behavioral therapy for insomnia (CBT-I and the new dual orexin receptor antagonist (DORA) pharmacologics.

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The evidence that an OX2R antagonist should be at least equivalent, or perhaps superior, to a DORA for the treatment of insomnia is reviewed, with a view to finding the ideal orexin agent to achieve a balanced increase in REM and non-rapid eye movement (NREM) sleep.

Orexin Receptor Antagonism, a New Sleep-Enabling Paradigm: A Proof-of-Concept Clinical Trial

Almorexant consistently and dose‐dependently improved sleep variables and may offer a new treatment approach for primary insomnia.

Effects of the orexin receptor antagonist suvorexant on respiration during sleep in healthy subjects

The data from healthy subjects suggest that suvorexant lacks clinically important respiratory effects during sleep at doses greater than the maximum recommended dose for treating insomnia.

A randomized Phase 2 study to evaluate the orexin-2 receptor antagonist seltorexant in individuals with insomnia without psychiatric comorbidity

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Orexin receptor antagonists for the treatment of insomnia and potential treatment of other neuropsychiatric indications

The role of orexin receptor antagonists in disorders of sleep/wake and other potential neuropsychiatric conditions, with a focus on suvorexant, which is currently the only approved agent in this class, is outlined.

Lemborexant, A Dual Orexin Receptor Antagonist (DORA) for the Treatment of Insomnia Disorder: Results From a Bayesian, Adaptive, Randomized, Double-Blind, Placebo-Controlled Study.

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  • Medicine, Psychology
    Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine
  • 2017
Lemborexant doses ranging from 2.5-10 mg provided efficacy for the treatment of insomnia while minimizing next-morning residual sleepiness and subjects showed significant improvements in SE, subjective SE, LPS, and subjective sleep onset latency at the beginning and end of treatment.

The orexin antagonist SB-649868 promotes and maintains sleep in men with primary insomnia.

The data demonstrate the sleep-promoting properties of the orexin antagonist SB-649868 in male patients with insomnia.

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The data suggest that orexin receptor antagonism offers a novel approach to treating insomnia, and Class I evidence that suvorexant improves sleep efficiency over 4 weeks in nonelderly adult patients with primary insomnia.

Orexin 2 Receptor Antagonism is Sufficient to Promote NREM and REM Sleep from Mouse to Man

Selective OX2R antagonism is sufficient to promote REM and NREM sleep across species, similarly to that seen with dual orexin receptor antagonism.