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Media related to Orexin receptor antagonists at Wikimedia Commons
| GABAA receptor positive modulators |
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| Antihistamines (H1 receptor inverse agonists) |
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| Orexin receptor antagonists | |
| Melatonin receptor agonists | |
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An orexin receptor antagonist, or orexin antagonist, is a drug that inhibits the effect of orexin by acting as a receptor antagonist of one (selective orexin receptor antagonist or SORA) or both (dual orexin receptor antagonist or DORA) of the orexin receptors, OX1 and OX2. [1] Medical applications include treatment of sleep disorders such as insomnia. [2] [3]
Orexin receptor antagonists dose-dependently improve sleep parameters including latency to persistent sleep (LPS), wake after sleep onset (WASO), sleep efficiency (SE), total sleep time (TST), and sleep quality (SQ). [22] [23] [24] [25] [26]
Orexin receptor antagonists are not currently used as first-line treatments for insomnia due to cost and concerns about possible misuse liability. [27]
Suvorexant appears to be effective in the prevention of delirium. [9] [10]
Side effects of orexin receptor antagonists include somnolence, daytime sleepiness and sedation, headache, abnormal dreams, fatigue, and dry mouth. [22] [23] [24] [26] [25]
Rates of somnolence or fatigue with orexin receptor antagonists in clinical trials were 7% (vs. 3% with placebo) for suvorexant 15 to 20 mg, [28] 7 to 10% (vs. 1.3% for placebo) for lemborexant 5 to 10 mg, [29] and 5 to 6% (vs. 4% with placebo) for daridorexant 25 to 50 mg. [30]
Narcolepsy, a neurological disorder caused by orexin deficiency, is a contraindication to the use of orexin antagonists. [31]
The elimination half-lives of clinically used orexin receptor antagonists are 12 hours for suvorexant, about 17 to 19 hours ("effective" half-life) or 55 hours (terminal elimination half-life) for lemborexant, and 6 to 10 hours for daridorexant. [8] The elimination half-lives of investigational orexin receptor antagonists are 2 to 3 hours for seltorexant and about 1.5 to 3 hours for vornorexant. [8] [32]
The pharmacokinetics of suvorexant are significantly affected by age, sex, and other factors, leading to increased blood concentrations in female, obese, and older patients. [7] These factors do not significantly affect the pharmacokinetics of lemborexant [7] or daridorexant. [33]
All three marketed orexin antagonists do not need to be dose adjusted in patients with reduced renal function, as the pharmacokinetic profiles of these medications are not significantly affected. [34] [33] [35] In patients with moderate to severe hepatic impairment, dose adjustments of these medications may be necessary. [36]
Filorexant was studied for but was not found to be effective in the treatment of diabetic neuropathy, migraine, and major depressive disorder in phase 2 clinical trials. [37] [38] [39] Seltorexant is under development for treatment of major depressive disorder however and is in phase 3 trials for this indication. [40] Also, suvorexant is in a phase 4 trial for use as an adjunct to antidepressant therapy in people with major depressive disorder and residual insomnia. [40] [41] [42]
Media related to Orexin receptor antagonists at Wikimedia Commons