List of investigational insomnia drugs

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 It is likely to become outdated with time.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]
  • Fazamorexant (YZJ-1139) – orexin OX1 and OX2 receptor antagonist[4]
  • Vornorexant (ORN-0829; TS-142) – orexin OX1 and OX2 receptor antagonist[5]
  • Zuranolone (BIIB-125; S-812217; SAGE-217; SGE-797; Zurzuvae) – GABAA receptor positive allosteric modulator and neurosteroid[6]

Phase 2

  • Lumateperone (Caplyta; ITI-007; ITI-722) – atypical antipsychotic (non-selective monoamine receptor modulator)[7]
  • Pimavanserin (Nuplazid; ACP-103; BVF-048) – serotonin 5-HT2A receptor antagonist[8]
  • Piromelatine (Neu-P11) – melatonin MT1 and MT2 receptor agonist, serotonin 5-HT1A and 5-HT1D receptor agonist, and serotonin 5-HT2B receptor antagonist[9]
  • Seltorexant (JNJ-42847922; JNJ-7922; MIN-202) – orexin OX2 receptor antagonist[10]
  • Sunobinop (IMB-115; IT-1315; RSC117957; S-117957; V-117957) – nociceptin receptor agonist[11]
  • Tasipimidine (ODM-105) – α2A-adrenergic receptor agonist[12]
  • 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[13]

Phase 1/2

  • SVT-4A1011 – microbiome modulator and live microbial therapeutic[14]

Preclinical

Not under development

No development reported

  • Filorexant (MK-6096) – orexin OX1 and OX2 receptor antagonist[19]
  • HEC-83518 – orexin receptor antagonist[20][21]
  • IN-AQUL-001 – undefined mechanism of action[22][23]
  • JNJ-48816274 – orexin OX2 receptor antagonist[24]
  • Lorediplon (GF-015535-00) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/pyrazolopyrimidine[25]
  • MK-1064 – orexin OX2 receptor antagonist[26]
  • Research programme: psychophysiological insomnia therapeutics - Neurim Pharmaceuticals – melatonin and serotonin receptor agonists[27]
  • Zolpidem topical gel (TR-396) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug[28]

Discontinued

  • ACT-462206 – orexin OX1 and OX2 receptor antagonist[29]
  • Adipiplon (NG-273) – GABAA receptor positive allosteric modulator[30]
  • ADX-10061 (NNC 01-0687; CEE-03-310; NNC-687) – dopamine D1 receptor antagonist[31][32][33]
  • Almorexant (ACT-078573) – orexin OX1 and OX2 receptor antagonist[34]
  • ANPH-101 – undefined mechanism of action[35]
  • Atagabalin (PD-0200390) – gabapentinoid (α2δ voltage-gated calcium channel ligand)[36]
  • Eplivanserin (Ciltyri; Sliwens; SR–46349; SR–46349B; SR–46615A) – serotonin 5-HT2A receptor antagonist[37]
  • Esmirtazapine (ORG-50081; SCH-900265; (S)-mirtazapine) – histamine H1 receptor antagonist, serotonin 5-HT2 receptor antagonist, and α2-adrenergic receptor antagonist[38]
  • Gaboxadol (LU-02030; LU-2-030; MK-0928; OV-101; THIP) – GABAA receptor agonist[39]
  • GT-2203 – histamine H3 receptor agonist[40]
  • Indiplon (NBI-34060) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/pyrazolopyrimidine[41][42][43]
  • LY-2624803 (HY-10275) – histamine H1 receptor inverse agonist and serotonin 5-HT2A receptor antagonist[44]
  • Nabilone (Cesamet) – cannabinoid CB1 and CB2 receptor agonist[45]
  • NBI-75043 – antihistamine (histamine H1 receptor antagonist)[46]
  • Nelotanserin (APD-125; RVT-102) – serotonin 5-HT2A receptor antagonist[47]
  • NGD-962 – GABAA receptor modulator[48]
  • Paliperidone (Invega; JNS-007ER; RO-76477; 9-hydroxyrisperidone) – atypical antipsychotic (non-selective monoamine receptor modulator)[49]
  • PD-0299685 (PF-299685) – gabapentinoid (α2δ voltage-gated calcium channel ligand)[50]
  • Remimazolam (HR-7056; Byfavo) – GABAA receptor positive allosteric modulator and benzodiazepine[51]
  • Suvecaltamide (CX-8998; JZP-385; MK-8998) – T-type calcium channel inhibitor[52]
  • Tesamorelin (Egrifta; MDVTM; TH-9507; ThGRF 1-44) – growth hormone-releasing hormone (GHRH) receptor agonist[53]
  • Triazolam intranasal (Hypnostat; TGAR01H) – GABAA receptor positive allosteric modulator and benzodiazepine[54]
  • Volinanserin (M-100907; MDL-100907) – serotonin 5-HT2A receptor antagonist[55]

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[62]
  • Zaleplon (Sonata; Zerene; CL–284846; L–846; LJC–10846) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug[63]
  • Zolpidem extended-release (Ambien CR; FK-199B; Stilnox; Zolpidem XR) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug[64]
  • Zolpidem oral spray (Zolpimist) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/Z-drug[65]

Orexin receptor antagonists

  • Daridorexant (Quviviq; ACT-541468; nemorexant) – orexin OX1 and OX2 receptor antagonist[66]
  • Lemborexant (Dayvigo; E-2006) – orexin OX1 and OX2 receptor antagonist[67]
  • Suvorexant (Belsomra; MK-4305) – orexin OX1 and OX2 receptor antagonist[68]

Melatonin receptor agonists

  • Melatonin controlled-release (Circadin; Orlogin; PedPRM; Slenyto; KI-1001) – melatonin MT1 and MT2 receptor agonist[69]
  • Ramelteon (Rozerem; TAK-375) – melatonin MT1 and MT2 receptor agonist[70]

Other drugs

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".
  2. ^ "Brexpiprazole - Lundbeck/Otsuka - AdisInsight".
  3. ^ "Diphenhydramine/Lorazepam/Zolpidem - Eusol Biotech - AdisInsight".
  4. ^ "YZJ 1139 - AdisInsight".
  5. ^ "Vornorexant - Taisho Pharmaceutical - AdisInsight".
  6. ^ "Zuranolone - Biogen/SAGE Therapeutics - AdisInsight".
  7. ^ "Lumateperone - Intra-Cellular Therapies - AdisInsight".
  8. ^ "Pimavanserin - ACADIA Pharmaceuticals - AdisInsight".
  9. ^ "Piromelatine - Neurim Pharmaceuticals - AdisInsight".
  10. ^ "Seltorexant - Janssen Research & Development/Minerva Neurosciences - AdisInsight".
  11. ^ "Sunobinop - Imbrium Therapeutics/Shionogi - AdisInsight".
  12. ^ "Tasipimidine - Orion - AdisInsight".
  13. ^ "Trazodone - Angelini Group/Labopharm - AdisInsight".
  14. ^ "SVT 4A1011 - AdisInsight".
  15. ^ "TPT 0601 - AdisInsight".
  16. ^ [1]
  17. ^ "Delving into the Latest Updates on YZG-331 with Synapse". Synapse. 8 May 2025. Retrieved 6 October 2025.
  18. ^ Tang B, Yu Y, Yu F, Fang J, Wang G, Jiang J, Han Q, Shi J, Zhang J (June 2022). "The mechanism study of YZG-331 on sedative and hypnotic effects". Behav Brain Res. 428 113885. doi:10.1016/j.bbr.2022.113885. PMID 35398229.
  19. ^ "Filorexant - AdisInsight".
  20. ^ "HEC 83518 - AdisInsight".
  21. ^ [2]
  22. ^ "IN AQUL 001 - AdisInsight".
  23. ^ "Delving into the Latest Updates on IN-AQUL-001 with Synapse".
  24. ^ "JNJ 48816274 - AdisInsight".
  25. ^ "Lorediplon - Ferrer - AdisInsight".
  26. ^ "MK 1064 - AdisInsight".
  27. ^ "Research programme: Psychophysiological insomnia therapeutics - Neurim Pharmaceuticals - AdisInsight".
  28. ^ "Zolpidem topical gel - Tritech Biopharmaceuticals - AdisInsight".
  29. ^ "ACT 462206 - AdisInsight".
  30. ^ "Adipiplon - AdisInsight".
  31. ^ "ADX 10061 - AdisInsight".
  32. ^ Eder DN (February 2002). "CEE-03-310 CeNeS pharmaceuticals". Curr Opin Investig Drugs. 3 (2): 284–288. 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].
  33. ^ Eder DN, Zdravkovic M, Wildschiødtz G (2003). "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. doi:10.1016/s0022-3956(03)00007-4. PMID 12765853.
  34. ^ "Almorexant - AdisInsight".
  35. ^ "ANPH 101 - AdisInsight".
  36. ^ "Atagabalin - AdisInsight".
  37. ^ "Eplivanserin - AdisInsight".
  38. ^ "Esmirtazapine - AdisInsight".
  39. ^ "Gaboxadol - Lundbeck A/S - AdisInsight".
  40. ^ "GT 2203 - AdisInsight".
  41. ^ "Delving into the Latest Updates on Indiplon with Synapse".
  42. ^ [3]
  43. ^ "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. Retrieved 17 September 2025.
  44. ^ "LY 2624803". AdisInsight. 5 November 2023. Retrieved 6 October 2025.
  45. ^ "Nabilone - AdisInsight".
  46. ^ "NBI 75043 - AdisInsight".
  47. ^ "Nelotanserin - Sio Gene Therapies - AdisInsight".
  48. ^ "NGD 962 - AdisInsight".
  49. ^ "Paliperidone - Johnson & Johnson - AdisInsight".
  50. ^ "PD 0299685 - AdisInsight".
  51. ^ "Remimazolam tosylate - Jiangsu Hengrui Medicine - AdisInsight".
  52. ^ "Suvecaltamide - Merck & Co - AdisInsight".
  53. ^ "Tesamorelin - Theratechnologies - AdisInsight".
  54. ^ "Triazolam intranasal - Fabre Kramer - AdisInsight".
  55. ^ "Volinanserin - AdisInsight".
  56. ^ "Dimdazenil - Evotec/Zhejiang Jingxin Pharmaceutical - AdisInsight".
  57. ^ Syed YY (May 2024). "Dimdazenil: First Approval". Drugs. 84 (5): 607–611. doi:10.1007/s40265-024-02020-9. PMID 38546956.
  58. ^ Wang W, Fu W, Zhu H, Ma J, Zhang J, Qi J (2024). "Progress in GABAA receptor agonists for insomnia disorder". Front Pharmacol. 15 1432726. doi:10.3389/fphar.2024.1432726. PMC 11573549. PMID 39564117.
  59. ^ "Quazepam - AdisInsight".
  60. ^ a b Moniri NH (November 2019). "Reintroduction of quazepam: an update on comparative hypnotic and adverse effects". Int Clin Psychopharmacol. 34 (6): 275–285. doi:10.1097/YIC.0000000000000277. PMID 31274695.
  61. ^ a b "Drugs for chronic insomnia". Med Lett Drugs Ther. 65 (1667): 1–6. January 2023. doi:10.58347/tml.2023.1667a. PMID 36630579.
  62. ^ "Eszopiclone - Sumitomo Pharma America - AdisInsight".
  63. ^ "Zaleplon - Pfizer - AdisInsight".
  64. ^ "Zolpidem extended release - Cosette Pharmaceuticals/Sanofi-aventis - AdisInsight".
  65. ^ "Zolpidem oral spray - Amherst Pharmaceuticals - AdisInsight".
  66. ^ "Daridorexant - Idorsia Pharmaceuticals - AdisInsight".
  67. ^ "Lemborexant - Eisai - AdisInsight".
  68. ^ "Suvorexant - Merck & Co - AdisInsight".
  69. ^ "Melatonin controlled-release - Neurim Pharmaceuticals - AdisInsight".
  70. ^ "Ramelteon - Takeda - AdisInsight".
  71. ^ "Doxepin low dose - Somaxon Pharmaceuticals - AdisInsight".
  72. ^ "Cannabidiol/Tetrahydrocannabinol - Zelira Therapeutics - AdisInsight".
  73. ^ Walsh JH, Maddison KJ, Rankin T, Murray K, McArdle N, Ree MJ, Hillman DR, Eastwood PR (November 2021). "Treating insomnia symptoms with medicinal cannabis: a randomized, crossover trial of the efficacy of a cannabinoid medicine compared with placebo". Sleep. 44 (11) zsab149. doi:10.1093/sleep/zsab149. PMC 8598183. PMID 34115851.
  74. ^ Krystal AD (December 2015). "New Developments in Insomnia Medications of Relevance to Mental Health Disorders". The Psychiatric Clinics of North America. 38 (4): 843–860. doi:10.1016/j.psc.2015.08.001. PMC 5972036. PMID 26600112.
  75. ^ a b c d e f g Atkin T, Comai S, Gobbi G (April 2018). "Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery". Pharmacological Reviews. 70 (2): 197–245. doi:10.1124/pr.117.014381. PMID 29487083. S2CID 3578916.
  76. ^ Naguy A (2016). "Clonidine Use in Psychiatry: Panacea or Panache". Pharmacology. 98 (1–2): 87–92. 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] .
  77. ^ Bamgbade OA, Tai-Osagbemi J, Bamgbade DO, Murphy-Akpieyi O, Fadire A, Soni NK, Mumporeze L (June 2022). "Clonidine is better than zopiclone for insomnia treatment in chronic pain patients". J Clin Sleep Med. 18 (6): 1565–1571. doi:10.5664/jcsm.9930. PMC 9163629. PMID 35112665.
  78. ^ Nguyen M, Tharani S, Rahmani M, Shapiro M (March 2014). "A review of the use of clonidine as a sleep aid in the child and adolescent population". Clin Pediatr (Phila). 53 (3): 211–216. doi:10.1177/0009922813502123. PMID 24027233.
  79. ^ Wilens TE, Biederman J, Spencer T (1994). "Clonidine for sleep disturbances associated with attention-deficit hyperactivity disorder". J Am Acad Child Adolesc Psychiatry. 33 (3): 424–426. doi:10.1097/00004583-199403000-00018. PMID 8169189.
  80. ^ Ordak M, Galazka A, Nasierowski T, Muszynska E, Bujalska-Zadrozny M (April 2023). "Reasons, Form of Ingestion and Side Effects Associated with Consumption of Amanita muscaria". Toxics. 11 (4): 383. Bibcode:2023Toxic..11..383O. doi:10.3390/toxics11040383. PMC 10142736. PMID 37112610.
  81. ^ Hartwig J, Kendrick J, Ahmad G, Cook J, Matthews DB, Sharma P (2025). "Exploring User Experiences with Amanita muscaria: A Thematic Analysis of Reddit Online Forum Discussions". Subst Use Misuse. 60 (7): 952–961. doi:10.1080/10826084.2025.2476141. PMID 40057818.
  82. ^ King JD (January 2025). "Promethazine is not a good option to aid sleep quality, especially for people using psychiatric services". BJPsych Bull: 1–3. doi:10.1192/bjb.2024.108. PMID 39758034.
  83. ^ Ried K, Tamanna T, Matthews S, Sali A (June 2023). "Medicinal cannabis improves sleep in adults with insomnia: a randomised double-blind placebo-controlled crossover study". J Sleep Res. 32 (3) e13793. doi:10.1111/jsr.13793. PMID 36539991.
  84. ^ Memi E, Pavli P, Papagianni M, Vrachnis N, Mastorakos G (August 2024). "Diagnostic and therapeutic use of oral micronized progesterone in endocrinology". Rev Endocr Metab Disord. 25 (4): 751–772. doi:10.1007/s11154-024-09882-0. PMC 11294403. PMID 38652231.
  85. ^ Sutanto CN, Loh WW, Kim JE (January 2022). "The impact of tryptophan supplementation on sleep quality: a systematic review, meta-analysis, and meta-regression". Nutr Rev. 80 (2): 306–316. doi:10.1093/nutrit/nuab027. PMID 33942088.
  86. ^ Maffei ME (December 2020). "5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology". Int J Mol Sci. 22 (1): 181. doi:10.3390/ijms22010181. PMC 7796270. PMID 33375373.
This article is issued from Wikipedia. The text is available under Creative Commons Attribution-Share Alike 4.0 unless otherwise noted. Additional terms may apply for the media files.