<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2d1 20170631//EN" "JATS-journalpublishing1.dtd">
      <Volume-Issue>Volume 15, Issue 02, 2023</Volume-Issue>
      <Season>April- June</Season>
      <ArticleType>Pharmacy Practice</ArticleType>
      <ArticleTitle>Daridorexant: A drug to treat insomnia</ArticleTitle>
      <Abstract>In this review, we have explained the drug “Daridorexant” which is been used for the treatment of insomnia. Clinical research has shown, however, that individuals with insomnia have inconsistent reporting of subjective (i.e., self-reported diaries) and objective (i.e., polysomnography) estimations of their sleep characteristics. Idorsia Pharmaceuticals Ltd. is developing daridorexant (Quviviq™), an orally given dual orexin Type 1 and Type 2 (OX1 and OX2) receptor antagonist (DORA), for the treatment of insomnia. Daridorexant was chosen from a pool of medication candidates because it had estimated effect duration of 8 h at a dosage of 25 mg and a half-life designed to minimize residual effects that might impede daytime functioning. Symptoms have been self-reported by approximately 30% of the general population and can cause a wide range of daily impacts such as fatigue, decreased energy, mood changes, and cognitive impairments. We have explained the pharmacokinetics and pharmacodynamics profile of Daridorexant. It preferentially targets orexin neurons and inhibits downstream neuronal pathways that promote wakefulness; however, it does not affect neuronal pathways that induce adverse effects found with positive allosteric gamma-aminobutyric acid-A receptor modulators. In the context of arrestin-mediated pathways, the possibility of biased signaling is being investigated. The drugs used in the orexinergic system are also included in this review.</Abstract>
      <Keywords>Allosteric gamma-aminobutyric acid-A receptor modulators, Arrestin-mediated pathway, Daridorexant, Insomnia, Oxinergic system</Keywords>
        <Abstract>https://isfcppharmaspire.com/ubijournal-v1copy/journals/abstract.php?article_id=14811&amp;title=Daridorexant: A drug to treat insomnia</Abstract>
        <References>1. Van Someren EJ. Brain mechanisms of insomnia: New  perspectives on causes and consequences. Physiol Rev 2021;101:995-1046.&#13;
2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Vol. 21. United States: American Psychiatric Association; 2013. p. 591-643.&#13;
3. Guan NC, Abousheishaa AA. Commentary: Validation of the somatic symptom Disorder-B criteria scale for adults in South Korea. Alpha Psychiatry 2022;23:235-6.&#13;
4. Riemann D, Benz F, Dressle RJ, Espie CA, Johann AF, Blanken TF, et al. Insomnia disorder: State of the science and challenges for the future. J Sleep Res 2022;31:e13604.&#13;
5. Herring WJ, Roth T, Krystal AD, Michelson D. Orexin receptor antagonists for the treatment of insomnia and potential treatment of other neuropsychiatric indications. J Sleep Res 2019;28:e12782.&#13;
6. Huang W, Li Z, Wu S, Hong J, Wen G. Small-world network of patients with primary insomnia: A restingstate functional magnetic resonance imaging study. Nan Fang Yi Ke Da Xue Xue Bao 2021;41:424-9.&#13;
7. Harvey AG, Tang NK. (Mis) perception of sleep in insomnia: A puzzle and a resolution. Psychol Bull 2012;138:77-101.&#13;
8. Wilson SJ, Nutt D, Alford C, Argyropoulos S, Baldwin DS, Bateson A, et al. British Association for Psychopharmacology consensus statement on evidencebased treatment of insomnia, parasomnias, and circadian rhythm disorders. J Psychopharmacol 2010;24:1577-601.&#13;
9. Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: An American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med 2017;13:307-49.&#13;
10. Scammell TE, Winrow CJ. Orexin receptors: Pharmacology and therapeutic opportunities. Annu Rev Pharmacol Toxicol 2011;51:243-66.&#13;
11. Markham A. Correction to daridorexant: First approval. Drugs 2022;82:841.&#13;
12. Ortega G. Iconicity and sign lexical acquisition: A review. Front Psychol 2017;8:1280. &#13;
13. Markham A. Daridorexant: First approval. Drugs 2022;82:601-7.&#13;
14. Mignot E, Mayleben D, Fietze I, Leger D, Zammit G, Bassetti CL, et al. Safety and efficacy of daridorexant in patients with insomnia disorder: Results from two multicentre, randomized, double-blind, placebocontrolled, phase 3 trials. Lancet Neurol 2022;21:125-39.&#13;
15. Roch C, Bergamini G, Steiner MA, Clozel M. Nonclinical pharmacology of daridorexant: A new dual orexin receptor antagonist for the treatment of insomnia. Psychopharmacology (Berl) 2021;238:2693-708.&#13;
16. Muehlan C, Boehler M, Brooks S, Zuiker R, van Gerven J, Dingemanse J. Clinical pharmacology of the dual orexin receptor antagonist ACT-541468 in elderly subjects: An exploration of pharmacokinetics, pharmacodynamics, and tolerability following singledose morning and repeated-dose evening administration. J Psychopharmacol 2020;34:326-35.&#13;
17. Ersoy A, Waller M. Drilling detritus and the operating parameters of thermally stable PDC core bits. Int J Rock Mech Min Sci 1997;34:1109-23.&#13;
18. Zammit G, Dauvilliers Y, Pain S, Kinter DS, Mansour Y, Kunz D. Daridorexant, a new dual orexin receptor antagonist, in elderly subjects with insomnia disorder. Neurology 2020;94:e2222-32.&#13;
19. Dauvilliers Y, Zammit G, Fietze I, Mayleben D, Kinter DS, Pain S, et al. Daridorexant, a new dual orexin receptor antagonist to treat insomnia disorder. Ann Neurol 2020;87:347-56.&#13;
20. Carney CE, Edinger JD, Kuchibhatla M, Lachowski AM, Bogouslavsky O, Krystal AD, et al. Cognitive behavioral insomnia therapy for those with insomnia and depression: A randomized controlled clinical trial. Sleep 2017;40:zsx019.&#13;
21. Kukkonen JP, Leonard C. Orexin/hypocretin receptor signaling cascades. Br J Pharmacol 2014;171:314-31.&#13;
22. Janto K, Prichard JR, Pusalavidyasagar S. An update on dual orexin receptor antagonists and their potential role in insomnia therapeutics. J Clin Sleep Med 2018;14:1399-408.&#13;
23. Hudgens S, Phillips-Beyer A, Newton L, Kinter DS, Benes H. Development and validation of the insomnia daytime symptoms and impacts questionnaire (IDSIQ). Patient 2021;14:249-68.&#13;
24. Muehlan C, Brooks S, Zuiker R, van Gerven J, Dingemanse J. Multiple-dose clinical pharmacology of ACT-541468, a novel dual orexin receptor antagonist, following repeated-dose morning and evening administration. Eur Neuropsychopharmacol 2019;29:847-57.&#13;
25. Gehin M, Wierdak J, Sabattini G, Sidharta PN, Dingemanse J. Effect of gastric pH and a moderate CYP3A4 inducer on the pharmacokinetics of&#13;
daridorexant, a dual orexin receptor antagonist. Br J Clin Pharmacol 2022;88:810-9.&#13;
26. Berger B, Brooks S, Zuiker R, Richard M, Muehlan C, Dingemanse J. Pharmacological interactions between the dual orexin receptor antagonist daridorexant and ethanol in a double-blind, randomized, placebo-controlled, double-dummy, four-way crossover phase I study in healthy subjects. CNS Drugs 2020;34:1253-66.&#13;
27. Bovin MJ, Marx BP, Weathers FW, Gallagher MW, Rodriguez P, Schnurr PP, et al. Psychometric properties of the PTSD checklist for diagnostic and statistical manual of mental disorders-fifth edition (PCL-5) in veterans. Psychol Assess 2016;28:1379-91.&#13;
28. Benca RM, Cirelli C, Rattenborg NC, Tononi G. Basic Science of Sleep. In: Comprehensive Textbook of Psychiatry. Philadelphia, PA: Lippincott, Williams, and Williams; 2004, p. 280-94.&#13;
29. Boutrel B, Koob GF. What keeps us awake: The neuropharmacology of stimulants and wakefulnesspromoting medications. Sleep 2004;27:1181-94.&#13;
30. Xu TR, Yang Y, Ward R, Gao L, Liu Y. Orexin receptors: Multi-functional therapeutic targets for sleeping disorders, eating disorders, drug addiction, cancers, and other physiological disorders. Cell Signal 2013;25:2413-23.&#13;
31. Baumann CR, Bassetti CL. Hypocretins (orexins) and sleep-wake disorders. Lancet Neurol 2005;4:673-82.&#13;
32. Hahn B, Robinson B, Geng J, Bansal S, Luck S, Gold J. ACNP 60th Annual Meeting: Poster Abstracts P551– P830. Biochem Biophys Res Commun 2018;503:1973-9.&#13;
33. Treiber A, de Kanter R, Roch C, Gatfield J, Boss C, von Raumer M, et al. The use of physiology-based pharmacokinetic and pharmacodynamic modeling in the discovery of the dual orexin receptor antagonist ACT- 541468. J Pharmacol Exp Ther 2017;362:489-503.&#13;
34. Kunz D, Dauvilliers Y, Benes H, Garcand;iacute;a-Borreguero D, Plazzi G, Kinter DS, et al. Long-term safety and tolerability of daridorexant in patients with insomnia disorder. CNS Drugs 2023;37:93-106.&#13;
35. Ohno K, Sakurai T. Orexin neuronal circuitry: Role in the regulation of sleep and wakefulness. Front Neuroendocrinol 2008;29:70-87.&#13;
36. Sun Y, Tisdale RK, Kilduff TS. Hypocretin/orexin receptor pharmacology and sleep phases. Front Neurol Neurosci 2021;45:22-37.&#13;
37. Kumar A, Chanana P, Choudhary S. Emerging role of orexin antagonists in insomnia therapeutics: An update on SORAs and DORAs. Pharmacol Rep 2016;68:231-42.&#13;
38. Equihua AC, De La Herrand;aacute;n-Arita AK, Drucker-Colin R. Orexin receptor antagonists as therapeutic agents for insomnia. Front Pharmacol 2013;4:163.&#13;
39. Al-Kuraishy HM, Abdulhadi MH, Hussien NR, Al-Niemi MS, Rasheed HA, Al-Gareeb AI. Involvement of orexinergic system in psychiatric and neurodegenerative disorders: A scoping review. Brain Circ 2020;6:70-80.&#13;
40. Al-Kuraishy H, Abdulhadi M, Hussien N, Al-Niemi M, Rasheed H, Al-Gareeb A. Involvement of an orexinergic system in psychiatric and neurodegenerative disorders: A scoping review. Brain Circ 2020;6:70-80.&#13;
41. Kimura H, Ishikawa T. 0142 TAK-925, an orexin 2 receptor-selective agonist, enhanced cortical arousal in a narcolepsy mouse model different from effects of modafinil. Sleep 2020;43:A56.&#13;
42. Desarnaud F, Murillo-Rodriguez E, Lin L, Xu M, Gerashchenko D, Shiromani SN, et al. The diurnal rhythm of hypocretin in young and old F344 rats. Sleep 2004;27:851-6.&#13;
43. Tobaldini E, Nobili L, Strada S, Casali KR, Braghiroli A, Montano N. Heart rate variability in normal and pathological sleep. Front Physiol 2013;4:294.&#13;
44. Bruni O, Ferini-Strambi L, Giacomoni E, Pellegrino P. Herbal remedies and their possible effect on the GABAergic system and sleep. Nutrients 2021;13:530.&#13;
45. Glaum P, Simao MC, Vaidya C, Fitch G, Iulinao B. Big city Bombus: Using natural history and land-use history to find significant environmental drivers in bumble-bee declines in urban development. R Soc Open Sci 2017;4:170156.&#13;
46. Chai F, Johnson KS, Claustre H, Xing X, Wang Y, Boss E, et al. Monitoring ocean biogeochemistry with autonomous platforms. Nat Rev Earth Environ 2020;1:315-26.&#13;
47. Tomczyk S, Muehlan H, Freitag S, Stolzenburg S, Schomerus G, Schmidt S. Is knowledge “half the battle”? The role of depression literacy in help-seeking among a non-clinical sample of adults with currently untreated mental health problems. J Affect Disord 2018;238:289-96.&#13;
48. Ziemichand;oacute;d W, Grabowska K, Kurowska A, Bia?a G. A comprehensive review of daridorexant, a dual-orexin receptor antagonist as a new approach for the treatment of insomnia. Molecules 2022;27:6041.&#13;
49. Edinger JD, Means MK. Cognitive-behavioral therapy for primary insomnia. Clin Psychol Rev 2005;25:539-58.&#13;
50. Wilson S, Anderson K, Baldwin D, Dijk DJ, Espie A, Espie C, et al. British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias, and circadian rhythm disorders: An update. J Psychopharmacol 2019;33:923-47.&#13;
51. Zammit G, Erman M, Wang-Weigand S, Sainati S, Zhang J, Roth T. Evaluation of the efficacy and safety of ramelteon in subjects with chronic insomnia. J Clin Sleep Med 2007;3:495-504.&#13;
52. Rybarczyk B, Lund HG, Garroway AM, Mack L. Cognitive behavioral therapy for insomnia in older adults: background, evidence, and overview of the treatment protocol. Clin Gerontol 2013;36:70-93.</References>