Orexin Receptor Antagonists and Insomnia

Wu, Xin; Xue, Tao; Chen, Zhouqing; Wang, Zhong; Chen, Gang

doi:10.1007/s11920-022-01357-w

Cited by 15 publications

(16 citation statements)

References 71 publications

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“…In a systematic review and network meta-analysis by Xue et al 4 daridorexant did not show much improvement compared with suvorexant and lemborexant in terms of safety and efficacy. However, the review only included 2 phase 2 studies of daridorexant with 460 patients and did not analyze the newly published phase 3 trials.…”

Section: Data Selectionmentioning

confidence: 93%

“…4 Lemborexant was found to be more effective than suvorexant in regards to subjective TST, WASO, and time to sleep onset (TSO), but this difference was not statistically significant where lemborexant would be recommended over suvorexant. 4,35…”

Section: Data Selectionmentioning

confidence: 95%

“…4 From these large scale phase 3 trials, it was found that patients with insomnia on daridorexant 50 mg had improved daytime functioning, while both 25 mg and 50 mg of daridorexant improved sleep outcomes. 4…”

Section: Data Selectionmentioning

confidence: 99%

“…7,8 Currently, suvorexant, lemborexant, and daridorexant are the 3 DORAs that are approved for clinical use. 4 Suvorexant has demonstrated improvements in sleep quality in regards to WASO, LPS, and TST, but has reported adverse effects of somnolence, abnormal dreams, and fatigue. 4 Lemborexant was found to be more effective than suvorexant in regards to subjective TST, WASO, and time to sleep onset (TSO), but this difference was not statistically significant where lemborexant would be recommended over suvorexant.…”

Section: Relevance To Patient Care and Clinical Practicementioning

confidence: 99%

“…Insomnia is a common condition that is being diagnosed more frequently in adults in the United States, with symptoms including difficulty with sleep onset and sleep maintenance as well as wakefulness after sleep onset. [1][2][3][4] In the American Insomnia Survey conducted from 2008 to 2009, more than 50% of adults had difficulty sleeping and about 20% met the diagnosis criteria for insomnia. 3 Insomnia is associated with increased healthcare utilization and costs, as well as workplace injuries, traffic accidents, and work absenteeism.…”

Section: Introductionmentioning

confidence: 99%

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Daridorexant: Comprehensive Review of A New Oral Agent for the Treatment of Insomnia

Park¹,

PharmD²,

Cates³

2023

Ann Pharmacother

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Objective: To review the current pharmacology, pharmacokinetics/pharmacodynamics, safety, and efficacy of daridorexant in patients with insomnia. Data Sources: A literature search of PubMed (March 1, 2018, to October 19, 2022) and ClinicalTrials.gov search was conducted using the following terms: daridorexant and ACT-541468. Additional articles were identified by hand from references. Study selection and data extraction: We included English-language articles evaluating daridorexant pharmacology, efficacy, or safety in humans for the management of insomnia. Data synthesis: Daridorexant has a peak plasma concentration of 1-2 hours, terminal half-life of 8 hours, and absolute bioavailability of 61%. Wake after sleep onset (WASO) significantly decreased from baseline to months 1 and 3 in daridorexant 25 (–18.40 and –22.97 min, P < 0.0001) and 50 mg (–28.98 and –29.41 min, P < 0.0001) groups compared with placebo. Latency to persistent sleep (LPS) significantly decreased from baseline to months 1 and 3 for daridorexant 25 mg (–28.17 and –30.73 min, P = 0.0005 and P = 0.0015) and 50 mg (–31.20 and –34.80 min, P < 0.0001). Relevance to patient care and clinical practice in comparison to existing agents: Daridorexant can be administered in diverse patient populations because of its tolerability and favorable safety profile. However, due to the lack of large scale studies that directly compare dual orexin receptor antagonists (DORAs), there is not enough data to recommend 1 DORA over another. Conclusions: Daridorexant is well tolerated and has demonstrated significant reductions in LPS and WASO in the treatment of insomnia in adult patients.

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Section: Data Selectionmentioning

confidence: 93%

Section: Data Selectionmentioning

confidence: 95%

Section: Data Selectionmentioning

confidence: 99%

Section: Relevance To Patient Care and Clinical Practicementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Daridorexant: Comprehensive Review of A New Oral Agent for the Treatment of Insomnia

Park¹,

PharmD²,

Cates³

2023

Ann Pharmacother

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orexin B alleviates sepsis‐associated lung injury through the attenuation of pulmonary endothelial barrier dysfunction by regulating the rho‐associated coiled‐coil containing protein kinase 2/zonula occludens‐1 (ROCK2/ZO‐1) axis

Wang,

Wan,

2024

Biotech and App Biochem

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Dysfunction of the alveolar endothelial barrier plays a crucial role in the pathogenesis of septic acute lung injury (ALI). orexin B is a neuropeptide derived from orexin neurons in the lateral hypothalamus and has multiple biological functions. However, the physiological function of orexin B in sepsis is less reported. Here, we aimed to explore the protective effects of orexin B in sepsis‐induced ALI and its underlying mechanisms. In this study, we established an ALI in vivo animal model in mice using cecal ligation and puncture (CLP) and an in vitro ALI model using mouse lung microvascular endothelial cells (MLMECs) induced with lipopolysaccharides (LPS). The animal experiments involved four groups: Sham, Sham+orexin B, CLP, CLP+orexin B. First, our results demonstrate that the levels of serum orexin B but not orexin A were reduced in septic mice. Correspondingly, the expression of orexin type 2 receptor (OX2R), but not orexin type 1 receptor (OX1R), was reduced in the lung tissue of septic mice. Administration of orexin B decreased the mortality in sepsis mice and improved M‐CASS scores. Hematoxylin–eosin (H&E) staining assay demonstrated that administration of orexin B ameliorated histopathological lung injury. orexin B was also found to inhibit the inflammatory response in the lung tissues of septic mice by reducing the expression of tumor necrosis factor α (TNF‐α), interleukin 6 (IL‐6), and recombinant chemokine C‐X‐C‐motif ligand 15 (CXCL15). Additionally, the total cell count and neutrophils in bronchoalveolar lavage fluid (BALF) were reduced by orexin B. Notably, orexin B alleviated vascular endothelial permeability in mice lung tissue by increasing the expression of the tight junction protein zonula occludens‐1 (ZO‐1) and occludin. In vitro experiments demonstrated that orexin B prevented LPS‐induced endothelial permeability in mouse lung microvascular endothelial cells (MLMECs) by upregulating the expression of ZO‐1 and occludin. These effects are mediated by rho‐associated coiled‐coil containing protein kinase 2 (ROCK2). Based on these findings, we conclude that orexin B alleviates sepsis‐induced ALI by ameliorating endothelial permeability of lung microvascular endothelial cells.

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Effects of methamphetamine on actigraphy-based sleep parameters in female rhesus monkeys: Orexin receptor mechanisms

Borgatti,

Rowlett,

Berro

2024

Drug and Alcohol Dependence

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Orexin Receptor Antagonists and Insomnia

Cited by 15 publications

References 71 publications

Daridorexant: Comprehensive Review of A New Oral Agent for the Treatment of Insomnia

Daridorexant: Comprehensive Review of A New Oral Agent for the Treatment of Insomnia

orexin B alleviates sepsis‐associated lung injury through the attenuation of pulmonary endothelial barrier dysfunction by regulating the rho‐associated coiled‐coil containing protein kinase 2/zonula occludens‐1 (ROCK2/ZO‐1) axis

Effects of methamphetamine on actigraphy-based sleep parameters in female rhesus monkeys: Orexin receptor mechanisms

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