Chemistry:List of investigational insomnia drugs

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Short description: Investigational insomnia drugs
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This is a list of investigational insomnia drugs, or drugs that are currently under development for clinical use for the treatment of insomnia but are not yet approved. They may also be referred to as investigational hypnotics.

Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses. The format of list items is "Name (Synonyms) – Mechanism of Action [Reference]".

This list was last comprehensively updated in September 2025. It is likely to become outdated with time.

Under development

Preregistration

  • Tasimelteon (Hetlioz; BMS-214778; VEC-162) – melatonin MT1 and MT2 receptor agonist[1]

Phase 3

  • Brexpiprazole (Rexulti; Lu-AF41156; OPC-34712; OPDC-34712) – atypical antipsychotic (non-selective monoamine receptor modulator)[2]
  • Diphenhydramine/lorazepam/zolpidem (SM-1; SM1) – combination of diphenhydramine (antihistamine and anticholinergic), lorazepam (benzodiazepine and GABAA receptor positive allosteric modulator), and zolpidem (nonbenzodiazepine/Z-drug and GABAA receptor positive allosteric modulator)[3]
  • Zuranolone (BIIB-125; S-812217; SAGE-217; SGE-797; Zurzuvae) – GABAA receptor positive allosteric modulator and neurosteroid[4]

Phase 2

  • Dexmedetomidine buccal (RE-03) — α2-adrenergic receptor agonist[5]
  • Lumateperone (Caplyta; ITI-007; ITI-722) – atypical antipsychotic (non-selective monoamine receptor modulator)[6]
  • Pimavanserin (Nuplazid; ACP-103; BVF-048) – serotonin 5-HT2A receptor antagonist[7]
  • Piromelatine (Neu-P11) – melatonin MT1 and MT2 receptor agonist, serotonin 5-HT1A and 5-HT1D receptor agonist, and serotonin 5-HT2B receptor antagonist[8]
  • Seltorexant (JNJ-42847922; JNJ-7922; MIN-202) – orexin OX2 receptor antagonist[9]
  • Sunobinop (IMB-115; IT-1315; RSC117957; S-117957; V-117957) – nociceptin receptor agonist[10]
  • Trazodone extended-release (AF-1161; DDS-04A; Oleptro; Triticum AC; Trittico) – serotonin 5-HT1A receptor partial agonist, serotonin 5-HT2A and 5-HT2C receptor antagonist, α1- and α2-adrenergic receptor antagonist, weak serotonin reuptake inhibitor, and other actions[11]

Phase 1/2

  • SVT-4A1011 – microbiome modulator and live microbial therapeutic[12]

Preclinical

Not under development

No development reported

  • Filorexant (MK-6096) – orexin OX1 and OX2 receptor antagonist[17]
  • HEC-83518 – orexin receptor antagonist[18][19]
  • IN-AQUL-001 – undefined mechanism of action[20][21]
  • JNJ-48816274 – orexin OX2 receptor antagonist[22]
  • Lirequinil (RO-413696) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/benzoquinolizinone [23]
  • Lorediplon (GF-015535-00) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/pyrazolopyrimidine[24]
  • MK-1064 – orexin OX2 receptor antagonist[25]
  • Research programme: psychophysiological insomnia therapeutics - Neurim Pharmaceuticals – melatonin and serotonin receptor agonists[26]
  • Zolpidem topical gel (TR-396) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug[27]

Discontinued

  • ACT-462206 – orexin OX1 and OX2 receptor antagonist[28]
  • Adipiplon (NG-273) – GABAA receptor positive allosteric modulator[29]
  • ADX-10061 (NNC 01-0687; CEE-03-310; NNC-687) – dopamine D1 receptor antagonist[30][31][32]
  • Almorexant (ACT-078573) – orexin OX1 and OX2 receptor antagonist[33]
  • ANPH-101 – undefined mechanism of action[34]
  • Atagabalin (PD-0200390) – gabapentinoid (α2δ voltage-gated calcium channel ligand)[35]
  • Eplivanserin (Ciltyri; Sliwens; SR–46349; SR–46349B; SR–46615A) – serotonin 5-HT2A receptor antagonist[36]
  • Esmirtazapine (ORG-50081; SCH-900265; (S)-mirtazapine) – histamine H1 receptor antagonist, serotonin 5-HT2 receptor antagonist, and α2-adrenergic receptor antagonist[37]
  • Gaboxadol (LU-02030; LU-2-030; MK-0928; OV-101; THIP) – GABAA receptor agonist[38]
  • GT-2203 – histamine H3 receptor agonist[39]
  • Indiplon (NBI-34060) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/pyrazolopyrimidine[40][41][42]
  • LY-2624803 (HY-10275) – histamine H1 receptor inverse agonist and serotonin 5-HT2A receptor antagonist[43]
  • Nabilone (Cesamet) – cannabinoid CB1 and CB2 receptor agonist[44]
  • NBI-75043 – antihistamine (histamine H1 receptor antagonist)[45]
  • Nelotanserin (APD-125; RVT-102) – serotonin 5-HT2A receptor antagonist[46]
  • NGD-962 (NGD 96-2) – GABAA receptor modulator[47]
  • Paliperidone (Invega; JNS-007ER; RO-76477; 9-hydroxyrisperidone) – atypical antipsychotic (non-selective monoamine receptor modulator)[48]
  • PD-0299685 (PF-299685) – gabapentinoid (α2δ voltage-gated calcium channel ligand)[49]
  • Pruvanserin (EMD-281014; LY-2422347; LSN-2411347) – serotonin 5-HT2A receptor antagonist[50]
  • Remimazolam (HR-7056; Byfavo) – GABAA receptor positive allosteric modulator and benzodiazepine[51]
  • Seganserin (R-56413) – serotonin 5-HT2A and 5-HT2C receptor antagonist[52]
  • Suvecaltamide (CX-8998; JZP-385; MK-8998) – T-type calcium channel inhibitor[53]
  • Tasipimidine (ODM-105) – α2A-adrenergic receptor agonist[54]
  • Tesamorelin (Egrifta; MDVTM; TH-9507; ThGRF 1-44) – growth hormone-releasing hormone (GHRH) receptor agonist[55]
  • Tiagabine (A-70569; CEP-6671; Gabitril; NO-050328; NO-328) – GABA transporter 1 (GAT-1) blocker and GABA reuptake inhibitor[56]
  • Triazolam intranasal (Hypnostat; TGAR01H) – GABAA receptor positive allosteric modulator and benzodiazepine[57]
  • Volinanserin (M-100907; MDL-100907) – serotonin 5-HT2A receptor antagonist[58]

Formal development never or not yet started

Clinically used drugs

Approved drugs

GABAA receptor positive allosteric modulators

Benzodiazepines

Nonbenzodiazepines/Z-drugs

  • Eszopiclone (Esopiclone; Estorra; Lunesta; Lunivia; S-Zopiclone; SEP-0227018; SEP-190; SEP-225441) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug[69]
  • Zaleplon (Sonata; Zerene; CL–284846; L–846; LJC–10846) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug[70]
  • Zolpidem extended-release (Ambien CR; FK-199B; Stilnox; Zolpidem XR) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug[71]
  • Zolpidem oral spray (Zolpimist) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug[72]

Orexin receptor antagonists

  • Daridorexant (Quviviq; ACT-541468; nemorexant) – orexin OX1 and OX2 receptor antagonist[73]
  • Fazamorexant (Mengping; HY-901139; YZJ-1139) – orexin OX1 and OX2 receptor antagonist[74]
  • Lemborexant (Dayvigo; E-2006) – orexin OX1 and OX2 receptor antagonist[75]
  • Suvorexant (Belsomra; MK-4305) – orexin OX1 and OX2 receptor antagonist[76]
  • Vornorexant (Vorzzz; ORN-0829; TS-142) – orexin OX1 and OX2 receptor antagonist[77]

Melatonin receptor agonists

  • Melatonin controlled-release (Circadin; Orlogin; PedPRM; Slenyto; KI-1001) – melatonin MT1 and MT2 receptor agonist[78]
  • Ramelteon (Rozerem; TAK-375) – melatonin MT1 and MT2 receptor agonist[79]

Other drugs

  • Doxepin low dose (Silenor; SO-101) – antihistamine (histamine H1 receptor antagonist)[80]
  • Niaprazine (Nopron) – serotonin 5-HT2A receptor antagonist and α1-adrenergic receptor antagonist
  • Phenibut (Anvifen) – GABAB receptor agonist and gabapentinoid (α2δ voltage-gated calcium channel ligand)[81]
  • Tetrahydrocannabinol/cannabinol/cannabidiol (THC/CBN/CBD; Zenivol; ZTL-101) – combination of tetrahydrocannabinol (THC) (cannabinoid), cannabinol (CBN) (cannabinoid), and cannabidiol (CBD) (cannabinoid)[82][83]

Discontinued drugs

GABAA receptor positive allosteric modulators

Other drugs

  • Fenadiazole (phénadiazole; Hypnazol, Eudormil, Viodor) – unknown mechanism of action

Off-label drugs

See also

References

  1. ↑ "Tasimelteon - Vanda Pharmaceuticals - AdisInsight". https://adisinsight.springer.com/drugs/800024285. 
  2. ↑ "Brexpiprazole - Lundbeck/Otsuka - AdisInsight". https://adisinsight.springer.com/drugs/800029282. 
  3. ↑ "Diphenhydramine/Lorazepam/Zolpidem - Eusol Biotech - AdisInsight". https://adisinsight.springer.com/drugs/800044642. 
  4. ↑ "Zuranolone - Biogen/SAGE Therapeutics - AdisInsight". https://adisinsight.springer.com/drugs/800043382. 
  5. ↑ "Dexmedetomidine - Reconnect Labs - AdisInsight". https://adisinsight.springer.com/drugs/800080476. 
  6. ↑ "Lumateperone - Intra-Cellular Therapies - AdisInsight". https://adisinsight.springer.com/drugs/800026498. 
  7. ↑ "Pimavanserin - ACADIA Pharmaceuticals - AdisInsight". https://adisinsight.springer.com/drugs/800014997. 
  8. ↑ "Piromelatine - Neurim Pharmaceuticals - AdisInsight". https://adisinsight.springer.com/drugs/800032086. 
  9. ↑ "Seltorexant - Janssen Research & Development/Minerva Neurosciences - AdisInsight". https://adisinsight.springer.com/drugs/800040115. 
  10. ↑ "Sunobinop - Imbrium Therapeutics/Shionogi - AdisInsight". https://adisinsight.springer.com/drugs/800035863. 
  11. ↑ "Trazodone - Angelini Group/Labopharm - AdisInsight". https://adisinsight.springer.com/drugs/800020235. 
  12. ↑ "SVT 4A1011 - AdisInsight". https://adisinsight.springer.com/drugs/800065865. 
  13. ↑ "TPT 0601 - AdisInsight". https://adisinsight.springer.com/drugs/800082141. 
  14. ↑ [1]
  15. ↑ "Delving into the Latest Updates on YZG-331 with Synapse". 8 May 2025. https://synapse.patsnap.com/drug/5e65914168974601accb3e1169e4fb23. 
  16. ↑ "The mechanism study of YZG-331 on sedative and hypnotic effects". Behav Brain Res 428. June 2022. doi:10.1016/j.bbr.2022.113885. PMID 35398229. 
  17. ↑ "Filorexant - AdisInsight". https://adisinsight.springer.com/drugs/800031738. 
  18. ↑ "HEC 83518 - AdisInsight". https://adisinsight.springer.com/drugs/800060970. 
  19. ↑ [2]
  20. ↑ "IN AQUL 001 - AdisInsight". https://adisinsight.springer.com/drugs/800043802. 
  21. ↑ "Delving into the Latest Updates on IN-AQUL-001 with Synapse". https://synapse.patsnap.com/drug/17798ba73128457e9e640b1665bf7543. 
  22. ↑ "JNJ 48816274 - AdisInsight". https://adisinsight.springer.com/drugs/800047120. 
  23. ↑ "Lirequinil". 25 July 2006. https://adisinsight.springer.com/drugs/800001968. 
  24. ↑ "Lorediplon - Ferrer - AdisInsight". https://adisinsight.springer.com/drugs/800029512. 
  25. ↑ "MK 1064 - AdisInsight". https://adisinsight.springer.com/drugs/800043267. 
  26. ↑ "Research programme: Psychophysiological insomnia therapeutics - Neurim Pharmaceuticals - AdisInsight". https://adisinsight.springer.com/drugs/800028535. 
  27. ↑ "Zolpidem topical gel - Tritech Biopharmaceuticals - AdisInsight". https://adisinsight.springer.com/drugs/800049320. 
  28. ↑ "ACT 462206 - AdisInsight". https://adisinsight.springer.com/drugs/800035442. 
  29. ↑ "Adipiplon - AdisInsight". https://adisinsight.springer.com/drugs/800021866. 
  30. ↑ "ADX 10061 - AdisInsight". https://adisinsight.springer.com/drugs/800001476. 
  31. ↑ "CEE-03-310 CeNeS pharmaceuticals". Curr Opin Investig Drugs 3 (2): 284–288. February 2002. PMID 12020061. "CEE-03-310 is a selective dopamine D1-like receptor antagonist with no appreciable binding affinity for other receptors. Although originally developed by Novo Nordisk A/S as NNC-687 for the treatment of schizophrenia, the company changed its therapeutic focus in the mid-1990s and the full rights to CEE-03-310 and several related compounds were subsequently granted to CeNeS Pharmaceuticals in 1999. CeNeS is currently investigating the drug's potential in the treatment of insomnia and alcohol dependency [340965], [382293], [401496],[416026]. A phase II, double-blind, placebo-controlled trial of CEE-03-310 demonstrated a dose-dependent enhancement of NREM sleep at the beginning of the night without any effects on the quantity of REM sleep [410739].". 
  32. ↑ "Selective alterations of the first NREM sleep cycle in humans by a dopamine D1 receptor antagonist (NNC-687)". J Psychiatr Res 37 (4): 305–312. 2003. doi:10.1016/s0022-3956(03)00007-4. PMID 12765853. 
  33. ↑ "Almorexant - AdisInsight". https://adisinsight.springer.com/drugs/800017756. 
  34. ↑ "ANPH 101 - AdisInsight". https://adisinsight.springer.com/drugs/800016090. 
  35. ↑ "Atagabalin - AdisInsight". https://adisinsight.springer.com/drugs/800025525. 
  36. ↑ "Eplivanserin - AdisInsight". https://adisinsight.springer.com/drugs/800001948. 
  37. ↑ "Esmirtazapine - AdisInsight". https://adisinsight.springer.com/drugs/800021392. 
  38. ↑ "Gaboxadol - Lundbeck A/S - AdisInsight". https://adisinsight.springer.com/drugs/800014543. 
  39. ↑ "GT 2203 - AdisInsight". https://adisinsight.springer.com/drugs/800008938. 
  40. ↑ "Delving into the Latest Updates on Indiplon with Synapse". https://synapse.patsnap.com/drug/85d5b45ef48f49869991045efd3b768f. 
  41. ↑ [3]
  42. ↑ "Indiplon: Indiplon modified-release, Indiplon MR, NBI 34060, NBI 34060 modified-release, NBI 34060 MR". Drugs in R&D 3 (3): 197–199. 2002. doi:10.2165/00126839-200203030-00012. ISSN 1174-5886. PMID 12099167. http://link.springer.com/10.2165/00126839-200203030-00012. Retrieved 17 September 2025. 
  43. ↑ "LY 2624803". 5 November 2023. https://adisinsight.springer.com/drugs/800025492. 
  44. ↑ "Nabilone - AdisInsight". https://adisinsight.springer.com/drugs/800025856. 
  45. ↑ "NBI 75043 - AdisInsight". https://adisinsight.springer.com/drugs/800024034. 
  46. ↑ "Nelotanserin - Sio Gene Therapies - AdisInsight". https://adisinsight.springer.com/drugs/800021795. 
  47. ↑ "NGD 962 - AdisInsight". https://adisinsight.springer.com/drugs/800011482. 
  48. ↑ "Paliperidone - Johnson & Johnson - AdisInsight". https://adisinsight.springer.com/drugs/800020763. 
  49. ↑ "PD 0299685 - AdisInsight". https://adisinsight.springer.com/drugs/800021998. 
  50. ↑ "Pruvanserin". 19 August 2014. https://adisinsight.springer.com/drugs/800024525. 
  51. ↑ "Remimazolam tosylate - Jiangsu Hengrui Medicine - AdisInsight". https://adisinsight.springer.com/drugs/800039498. 
  52. ↑ "5-HT2 receptor subtypes: a family re-united?". Trends Pharmacol Sci 16 (3): 105–110. March 1995. doi:10.1016/s0165-6147(00)88991-9. PMID 7792930. 
  53. ↑ "Suvecaltamide - Merck & Co - AdisInsight". https://adisinsight.springer.com/drugs/800026091. 
  54. ↑ "Tasipimidine - Orion - AdisInsight". https://adisinsight.springer.com/drugs/800070674. 
  55. ↑ "Tesamorelin - Theratechnologies - AdisInsight". https://adisinsight.springer.com/drugs/800009566. 
  56. ↑ "Tiagabine". 24 October 2021. https://adisinsight.springer.com/drugs/800001613. 
  57. ↑ "Triazolam intranasal - Fabre Kramer - AdisInsight". https://adisinsight.springer.com/drugs/800014239. 
  58. ↑ "Volinanserin - AdisInsight". https://adisinsight.springer.com/drugs/800001847. 
  59. ↑ "The microbiota-gut-brain axis in sleep disorders". Sleep Med Rev 65. October 2022. doi:10.1016/j.smrv.2022.101691. PMID 36099873. "Tributyrin, as a butyrate pro-drug, improved NREM sleep in rats, an effect mediated through the vagus in the hepatoportal region [110]. A recent study in young subjects showed that sleep quality was positively associated with higher relative abundance of butyrate-producing genera [111].". 
  60. ↑ "Butyrate, a metabolite of intestinal bacteria, enhances sleep". Sci Rep 9 (1). May 2019. doi:10.1038/s41598-019-43502-1. PMID 31065013. Bibcode: 2019NatSR...9.7035S. "Oral gavage administration of tributyrin, a butyrate pro-drug, elicited an almost 50% increase in non-rapid-eye movement sleep (NREMS) in mice for 4 hours after the treatment. Similarly, intraportal injection of butyrate led to prompt and robust increases in NREMS in rats. In the first 6 hours after the butyrate injection, NREMS increased by 70%.". 
  61. ↑ "Gut microbiota regulate insomnia-like behaviors via gut-brain metabolic axis". Mol Psychiatry 30 (6): 2597–2611. June 2025. doi:10.1038/s41380-024-02867-0. PMID 39658705. "Tributyrin administration led to a significant 39.50% reduction of wakefulness during the post-administration period (Fig. 3C, F). The decrease in wakefulness was accompanied by a significant 100.05% increase in NREM sleep and a substantial 77.99% increase in REM sleep (Fig. 3D–F).". 
  62. ↑ "Dietary tributyrin supplementation in Parkinson's disease: An open-label target engagement study". Neurotherapeutics 23 (1). January 2026. doi:10.1016/j.neurot.2025.e00791. PMID 41271518. "Sleep and heart rate data obtained via Oura™ biometric ring monitoring were largely unremarkable, although deep sleep proportion increased significantly (on average, 21.9 % greater proportion of nightly deep sleep) as a function of treatment.". 
  63. ↑ "Dimdazenil - Evotec/Zhejiang Jingxin Pharmaceutical - AdisInsight". https://adisinsight.springer.com/drugs/800023883. 
  64. ↑ "Dimdazenil: First Approval". Drugs 84 (5): 607–611. May 2024. doi:10.1007/s40265-024-02020-9. PMID 38546956. https://figshare.com/articles/online_resource/Dimdazenil_First_Approval/25355965. 
  65. ↑ "Progress in GABAA receptor agonists for insomnia disorder". Front Pharmacol 15. 2024. doi:10.3389/fphar.2024.1432726. PMID 39564117. 
  66. ↑ "Quazepam - AdisInsight". https://adisinsight.springer.com/drugs/800001266. 
  67. ↑ 67.0 67.1 "Reintroduction of quazepam: an update on comparative hypnotic and adverse effects". Int Clin Psychopharmacol 34 (6): 275–285. November 2019. doi:10.1097/YIC.0000000000000277. PMID 31274695. 
  68. ↑ 68.0 68.1 "Drugs for chronic insomnia". Med Lett Drugs Ther 65 (1667): 1–6. January 2023. doi:10.58347/tml.2023.1667a. PMID 36630579. 
  69. ↑ "Eszopiclone - Sumitomo Pharma America - AdisInsight". https://adisinsight.springer.com/drugs/800012417. 
  70. ↑ "Zaleplon - Pfizer - AdisInsight". https://adisinsight.springer.com/drugs/800001408. 
  71. ↑ "Zolpidem extended release - Cosette Pharmaceuticals/Sanofi-aventis - AdisInsight". https://adisinsight.springer.com/drugs/800023980. 
  72. ↑ "Zolpidem oral spray - Amherst Pharmaceuticals - AdisInsight". https://adisinsight.springer.com/drugs/800020309. 
  73. ↑ "Daridorexant - Idorsia Pharmaceuticals - AdisInsight". https://adisinsight.springer.com/drugs/800044843. 
  74. ↑ "YZJ 1139 - AdisInsight". https://adisinsight.springer.com/drugs/800070010. 
  75. ↑ "Lemborexant - Eisai - AdisInsight". https://adisinsight.springer.com/drugs/800035210. 
  76. ↑ "Suvorexant - Merck & Co - AdisInsight". https://adisinsight.springer.com/drugs/800027707. 
  77. ↑ "Vornorexant - Taisho Pharmaceutical - AdisInsight". https://adisinsight.springer.com/drugs/800049420. 
  78. ↑ "Melatonin controlled-release - Neurim Pharmaceuticals - AdisInsight". https://adisinsight.springer.com/drugs/800018177. 
  79. ↑ "Ramelteon - Takeda - AdisInsight". https://adisinsight.springer.com/drugs/800014547. 
  80. ↑ "Doxepin low dose - Somaxon Pharmaceuticals - AdisInsight". https://adisinsight.springer.com/drugs/800021918. 
  81. ↑ "Phenibut: Review and Pharmacologic Approaches to Treating Withdrawal". J Clin Pharmacol 64 (6): 652–671. June 2024. doi:10.1002/jcph.2414. PMID 38339875. "β-Phenyl-γ-aminobutyric acid (phenibut) is an analog of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) that was first synthesized in Russia in the early 1960s. It is marketed as a nootropic (smart drug) to improve cognitive performance, and to treat generalized and social anxiety, insomnia, and alcohol withdrawal. [...] β-Phenyl-γ-aminobutyric acid (phenibut) is a glutamic acid analog, first synthesized by Perekalin and colleagues at the Herzen Pedagogic Institute in St Petersburg, Russia, in 1963.1 The brand names for phenibut include Anvifen, Citrocard, Fenibut, Noofen, and others.2,3 For over 50 years, phenibut has been available in Eastern European countries, including Belarus, Estonia, Kazakhstan, Latvia, Russia, and Ukraine, as a prescription medication. It is used to treat a variety of central nervous system disorders, including generalized and social anxiety, post-traumatic stress disorder (PTSD), depression, insomnia, vestibular disorders, alcohol withdrawal, stuttering, attention deficit hyperactivity disorder, motor tics, and restless leg syndrome.1,4,5". 
  82. ↑ "Cannabidiol/Tetrahydrocannabinol - Zelira Therapeutics - AdisInsight". https://adisinsight.springer.com/drugs/800057418. 
  83. ↑ "Treating insomnia symptoms with medicinal cannabis: a randomized, crossover trial of the efficacy of a cannabinoid medicine compared with placebo". Sleep 44 (11). November 2021. doi:10.1093/sleep/zsab149. PMID 34115851. 
  84. ↑ "New Developments in Insomnia Medications of Relevance to Mental Health Disorders". The Psychiatric Clinics of North America 38 (4): 843–860. December 2015. doi:10.1016/j.psc.2015.08.001. PMID 26600112. 
  85. ↑ 85.0 85.1 85.2 85.3 85.4 85.5 85.6 "Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery". Pharmacological Reviews 70 (2): 197–245. April 2018. doi:10.1124/pr.117.014381. PMID 29487083. 
  86. ↑ "Clonidine Use in Psychiatry: Panacea or Panache". Pharmacology 98 (1–2): 87–92. 2016. doi:10.1159/000446441. PMID 27161101. "Moreover, clonidine helps in the treatment of neuroleptic-induced akathisia, stimulant-induced insomnia and clozapine-induced sialorrhea. Moreover, clonidine seems to be an attractive option targeting insomnia in ADHD [10] and remain a good remedy for paediatric insomnia in general [10] , and a case series has also reported that clonidine seems to be beneficial and fairly well tolerated in intractable sleep disorders in children and young adults with neurodevelopmental disorders [11] .". 
  87. ↑ "Clonidine is better than zopiclone for insomnia treatment in chronic pain patients". J Clin Sleep Med 18 (6): 1565–1571. June 2022. doi:10.5664/jcsm.9930. PMID 35112665. 
  88. ↑ "A review of the use of clonidine as a sleep aid in the child and adolescent population". Clin Pediatr (Phila) 53 (3): 211–216. March 2014. doi:10.1177/0009922813502123. PMID 24027233. 
  89. ↑ "Clonidine for sleep disturbances associated with attention-deficit hyperactivity disorder". J Am Acad Child Adolesc Psychiatry 33 (3): 424–426. 1994. doi:10.1097/00004583-199403000-00018. PMID 8169189. 
  90. ↑ Ghanavatian, Shirin; Derian, Armen (28 August 2023). "Tizanidine". StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK519505/. "It is also prescribed off-label for migraine headaches, insomnia, and as an anticonvulsant. [...] Off-label Use [...] Refractory insomnia in spastic quadriplegic patients[7] [...] Tanaka H, Fukuda I, Miyamoto A, Oka R, Cho K, Fujieda K. [Effects of tizanidine for refractory sleep disturbance in disabled children with spastic quadriplegia]. No To Hattatsu. 2004 Nov;36(6):455-60. [PubMed]" 
  91. ↑ "α-Adrenergic receptor function, arousal and sleep: mechanisms and therapeutic implications". Pharmacopsychiatry 45 (6): 209–216. September 2012. doi:10.1055/s-0031-1299728. PMID 22290201. "Tizanidine is a centrally acting α2 -receptor agonist, structurally related to clonidine. [...] In a study by Tanaka et al. [ 75 ] tizanidine was used in children with spastic quadriplegia to treat refractory sleep disturbances. Tizanidine treatment improved sleep induction and/or maintenance in 61.9 % of the children.". 
  92. ↑ "Tizanidine in the management of spasticity and musculoskeletal complaints in the palliative care population". Am J Hosp Palliat Care 17 (1): 50–58. 2000. doi:10.1177/104990910001700111. PMID 11094920. "Tizanidine can cause sedation, which is minimized by dose titration. When taken at night, patients report improvement in getting to sleep and little drowsiness or "hangover sensation" upon waking. Tizanidine is potentially helpful to many palliative care patients with chronic muscle pain and sleep disturbances.". 
  93. ↑ "Reasons, Form of Ingestion and Side Effects Associated with Consumption of Amanita muscaria". Toxics 11 (4): 383. April 2023. doi:10.3390/toxics11040383. PMID 37112610. Bibcode: 2023Toxic..11..383O. 
  94. ↑ "Exploring User Experiences with Amanita muscaria: A Thematic Analysis of Reddit Online Forum Discussions". Subst Use Misuse 60 (7): 952–961. 2025. doi:10.1080/10826084.2025.2476141. PMID 40057818. 
  95. ↑ "Promethazine is not a good option to aid sleep quality, especially for people using psychiatric services". BJPsych Bull: 1–3. January 2025. doi:10.1192/bjb.2024.108. PMID 39758034. 
  96. ↑ "Medicinal cannabis improves sleep in adults with insomnia: a randomised double-blind placebo-controlled crossover study". J Sleep Res 32 (3). June 2023. doi:10.1111/jsr.13793. PMID 36539991. 
  97. ↑ "Diagnostic and therapeutic use of oral micronized progesterone in endocrinology". Rev Endocr Metab Disord 25 (4): 751–772. August 2024. doi:10.1007/s11154-024-09882-0. PMID 38652231. 
  98. ↑ "The impact of tryptophan supplementation on sleep quality: a systematic review, meta-analysis, and meta-regression". Nutr Rev 80 (2): 306–316. January 2022. doi:10.1093/nutrit/nuab027. PMID 33942088. 
  99. ↑ "5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology". Int J Mol Sci 22 (1): 181. December 2020. doi:10.3390/ijms22010181. PMID 33375373. 

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