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

TLDR
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
TLDR
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

TLDR
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.

TLDR
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.

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

TLDR
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

TLDR
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.

TLDR
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.

Sleep disorders and the hypothalamus.

NDT_A_297504 2549..2566

TLDR
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.

References

SHOWING 1-10 OF 40 REFERENCES

Orexin OX2 Receptor Antagonists as Sleep Aids.

TLDR
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

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

Differential Effects of a Dual Orexin Receptor Antagonist (SB-649868) and Zolpidem on Sleep Initiation and Consolidation, SWS, REM Sleep, and EEG Power Spectra in a Model of Situational Insomnia

TLDR
This dual orexin receptor antagonist exerts hypnotic activity, with effects on sleep structure and the EEG that are different from those of zolpidem.

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

TLDR
Investigation of the effect of seltorexant on sleep efficiency after single and multiple dose administration in subjects with insomnia disorder without psychiatric comorbidity resulted in a prolonged total sleep time, shorter latency to persistent sleep and wake after sleep onset.

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

TLDR
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.

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

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

Orexin receptor antagonism for treatment of insomnia

TLDR
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

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

Effects of Suvorexant, an Orexin Receptor Antagonist, on Respiration during Sleep In Patients with Obstructive Sleep Apnea.

  • Hong SunJ. Palcza M. Troyer
  • Medicine
    Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine
  • 2016
TLDR
Suvorexant 40 mg, twice the 20 mg maximum recommended dose for treating insomnia in the USA and Japan, does not appear to have clinically important respiratory effects during sleep in patients with mild to moderate OSA as assessed by mean AHI and SpO2.