List_of_investigational_antidepressants

List of investigational antidepressants

List of investigational antidepressants

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This is a list of investigational antidepressants, or antidepressants that are currently under development for clinical use in the treatment of mood disorders but are not yet approved.

All drugs listed are specifically under development for major depressive disorder (MDD) and/or treatment-resistant depression (TRD) unless noted otherwise. Other forms of depression may include bipolar depression and postpartum depression.

Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses.

Glutamatergics

NMDA receptor modulators

Negative modulator

  • Ketamine (PMI-100, PMI-150, R-107, SHX-001, SLS-002; TUR-002) – non-competitive NMDA receptor antagonist.[1] (hydroxynorketamine ((2R,6R)-HNK) – metabolite of ketamine which may be involved in ketamine's antidepressant-like effects in mice[2][3])
    • Arketamine (PCN-101, HR-071603) – unknown mechanism of action, indirect AMPA receptor activator[2][4]
    • Esketamine (Esketamine DPI, Falkieri, PG061) – non-competitive NMDA receptor antagonist – approved for TRD, specifically under development for bipolar depression and "depressive disorders"
  • Esmethadone (dextromethadone; REL-1017) – NMDA receptor antagonist open channel blocker[5]

Positive modulator

AMPA receptor modulators

GABAergics

GABAA receptor positive modulators

  • Zuranolone (SAGE-217) – GABAA receptor positive allosteric modulator – specifically under development for the treatment of MDD and postpartum depression[9]

Monoaminergics

Monoamine reuptake inhibitors

Monoamine reuptake inhibitors and receptor modulators

Monoamine receptor activators

Monoamine receptor inhibitors

  • Amisulpride (Aramisulpride/esamisulpride (85:15 ratio)) (SEP-4199) – 5-HT7 receptor antagonist (aramisulpride) and D2 and D3 receptor antagonist (esamisulpride) – specifically under development for the treatment of bipolar depression[14][15]
  • Brilaroxazine (RP-5063, RP-5000) – AA – specifically under development for the treatment of MDD[16]
  • Lumateperone (ITI-007, Caplyta) – AA – specifically under development for the treatment of MDD and bipolar.[17] Has been approved to treat BP 1 and BP 2 disorder under the brand name Caplyta.
  • Lurasidone (Latuda) – AA – specifically under development for the treatment of MDD
  • Pimavanserin (Nuplazid; ACP-103; BVF-048) – 5-HT2A receptor antagonist – specifically under development for the treatment of MDD[18]

Monoamine releasing agents

Cofactor in monoamine biosynthesis

Opioidergics

κ-Opioid receptor antagonists

Nociceptin receptor antagonists

Cholinergics

Muscarinic acetylcholine receptor modulators

Orexin receptor antagonists

OX1 receptor antagonists

OX2 receptor antagonists

Neurosteroids

Others

Mixed

Combinations

Not under development

The following notable drugs are of investigational interest as potential antidepressants but are not formally under clinical development for approval at this time:

See also

References

  1. [1]
    "Ketamine intranasal - Vyera Pharmaceuticals". adisinsight.springer.com. Archived from the original on 24 September 2017. Retrieved 7 May 2017.
  2. [2]
    Hashimoto K (October 2019). "Rapid-acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective". Psychiatry and Clinical Neurosciences. 73 (10): 613–627. doi:10.1111/pcn.12902. PMC 6851782. PMID 31215725.
  3. [3]
    Zanos P, Moaddel R, Morris PJ, Georgiou P, Fischell J, Elmer GI, et al. (May 2016). "NMDAR inhibition-independent antidepressant actions of ketamine metabolites". Nature. 533 (7604): 481–6. Bibcode:2016Natur.533..481Z. doi:10.1038/nature17998. PMC 4922311. PMID 27144355.
  4. [4]
    "Arketamine - Jiangsu Hengrui Medicine - AdisInsight".
  5. [5]
    "Dextromethadone - Relmada Therapeutics". adisinsight.springer.com. Retrieved 10 November 2018.
  6. [6]
    Burgdorf JS, Zhang XL, Stanton PK, Moskal JR, Donello JE (December 2022). "Zelquistinel Is an Orally Bioavailable Novel NMDA Receptor Allosteric Modulator That Exhibits Rapid and Sustained Antidepressant-Like Effects". The International Journal of Neuropsychopharmacology. 25 (12): 979–991. doi:10.1093/ijnp/pyac043. PMC 9743962. PMID 35882204.
  7. [7]
    "Gate Neurosciences Hones in on Precision Medicine with Expanded Research Operations Supporting Its Synaptic Function-Enhancing Molecules" (PDF). Gate Neurosciences, Inc. 3 May 2023. Retrieved 26 May 2023.
  8. [8]
    "Apimostinel". adisinsight.springer.com. Retrieved 7 May 2017.
  9. [9]
    "SAGE 217". adisinsight.springer.com. Retrieved 9 February 2018.
  10. [10]
    "PDC-1421". adisinsight.springer.com. Retrieved 24 March 2018.
  11. [11]
    "FKB 01MD". adisinsight.springer.com. Retrieved 7 May 2017.
  12. [12]
    "Pramipexole - Chase Therapeutics - AdisInsight". adisinsight.springer.com. Retrieved 2020-01-25.
  13. [13]
    "Product Discovery and Development". Chase Therapeutics. Retrieved 2020-01-25.
  14. [14]
    "SEP 4199 - AdisInsight".
  15. [15]
    Hopkins SC, Wilkinson S, Corriveau TJ, Nishikawa H, Nakamichi K, Loebel A, Koblan KS (May 2021). "Discovery of Non-racemic Amisulpride to Maximize Benefit/Risk of 5-HT7 and D2 Receptor Antagonism for the Treatment of Mood Disorders". Clin Pharmacol Ther. 110 (3): 808–815. doi:10.1002/cpt.2282. PMC 8453756. PMID 33961287.
  16. [16]
    "RP 5063". adisinsight.springer.com. Retrieved 7 May 2017.
  17. [17]
    "Lumateperone". adisinsight.springer.com. Retrieved 7 May 2017.
  18. [18]
    "Pimavanserin". adisinsight.springer.com. Retrieved 25 September 2017.
  19. [19]
    "Tramadol controlled release - e-Therapeutics". adisinsight.springer.com. Retrieved 7 May 2017.
  20. [20]
    "Another depression drug flops as e-Therapeutics tallies PhIIb data - FierceBiotech". www.fiercebiotech.com. 15 February 2016. Retrieved 28 August 2018.
  21. [21]
    "E-Therapeutics defends PhIIb fail, claiming drug has 'pretty much' the hoped-for profile - FierceBiotech". www.fiercebiotech.com. 17 February 2016. Retrieved 28 August 2018.
  22. [22]
    "Ademetionine". adisinsight.springer.com. Retrieved 7 May 2017.
  23. [23]
    "Aticaprant (JNJ-67953964, CERC-501, LY-2456302) - AdisInsight". adisinsight.springer.com. Retrieved 2022-08-29.
  24. [24]
    "BTRX 335140 - AdisInsight". adisinsight.springer.com. Retrieved 2020-01-25.
  25. [25]
    "BlackThorn Therapeutics Advances Phase 2 Clinical Development for Selective KOR Antagonist, BTRX-140, in Neuropsychiatric Disorders". BlackThorn Therapeutics. Archived from the original on 2020-01-25. Retrieved 2020-01-25.
  26. [26]
    "Buprenorphine/samidorphan". adisinsight.springer.com. Retrieved 7 May 2017.
  27. [27]
    "CVL-354". adisinsight.springer.com. Retrieved 2 February 2023.
  28. [28]
    "BTRX-246040". adisinsight.springer.com. Retrieved 24 March 2018.
  29. [29]
    "JNJ 61393215 - AdisInsight". adisinsight.springer.com. Retrieved 2020-01-25.
  30. [30]
    "A Study of JNJ-61393215 in the Treatment of Depression - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2020-01-25.
  31. [31]
    "JNJ 42847922". adisinsight.springer.com. Retrieved 7 May 2017.
  32. [32]
    "PH 10 nasal spray". adisinsight.springer.com. Retrieved 7 May 2017.
  33. [33]
    "Pregnenolone methyl ether". adisinsight.springer.com. Retrieved 7 May 2017.
  34. [34]
    "JNJ-54175446". adisinsight.springer.com. Retrieved 24 March 2018.
  35. [35]
    "NSI 189". adisinsight.springer.com. Retrieved 7 May 2017.
  36. [36]
    "NV 5138". adisinsight.springer.com. Retrieved 7 November 2018.
  37. [37]
    Duman RS (2018). "Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide". F1000Research. 7: 659. doi:10.12688/f1000research.14344.1. PMC 5968361. PMID 29899972.
  38. [38]
    Duman R, Kato T, Liu RJ, Duman C, Terwilliger R, Vlasuk G, Hahm S, Sajah E (November 2017). "Sestrin 2 Modulator NV-5138 Shows Ketamine-Like Rapid Antidepressant Effects via Direct Activation of mTORC1 Signaling" (PDF). Neuropsychopharmacology. 43: S195. doi:10.1038/npp.2017.264.
  39. [39]
    "TS 121". adisinsight.springer.com. Retrieved 7 May 2017.
  40. [40]
    "Xenon Pharmaceuticals".
  41. [41]
    Costi S, Han MH, Murrough JW (March 2022). "The Potential of KCNQ Potassium Channel Openers as Novel Antidepressants". CNS Drugs. 36 (3): 207–216. doi:10.1007/s40263-021-00885-y. PMID 35258812. S2CID 247294637.
  42. [42]
    Sakurai H, Yonezawa K, Tani H, Mimura M, Bauer M, Uchida H (July 2022). "Novel Antidepressants in the Pipeline (Phase II and III): A Systematic Review of the US Clinical Trials Registry". Pharmacopsychiatry. 55 (4): 193–202. doi:10.1055/a-1714-9097. PMC 9259184. PMID 35045580.
  43. [43]
    "Psilocybin". adisinsight.springer.com. Retrieved 26 October 2018.
  44. [44]
    "Cycloserine/lurasidone - NeuroRx". adisinsight.springer.com. Retrieved 7 May 2017.
  45. [45]
    "Deudextromethorphan". adisinsight.springer.com. Retrieved 7 May 2017.
  46. [46]
    Rosenblat JD, McIntyre RS (February 2018). "Efficacy and tolerability of minocycline for depression: A systematic review and meta-analysis of clinical trials". Journal of Affective Disorders. 227: 219–225. doi:10.1016/j.jad.2017.10.042. PMID 29102836.
  47. [47]
    Cohen IV, Makunts T, Atayee R, Abagyan R (May 2017). "Population scale data reveals the antidepressant effects of ketamine and other therapeutics approved for non-psychiatric indications". Scientific Reports. 7 (1): 1450. Bibcode:2017NatSR...7.1450C. doi:10.1038/s41598-017-01590-x. PMC 5431207. PMID 28469132.
  48. [48]
    Nagele P, Zorumski CF, Conway C (April 2018). "Exploring Nitrous Oxide as Treatment of Mood Disorders: Basic Concepts". Journal of Clinical Psychopharmacology. 38 (2): 144–148. doi:10.1097/JCP.0000000000000837. PMC 5825282. PMID 29360650.
  49. [49]
    Lener MS, Kadriu B, Zarate CA (March 2017). "Ketamine and Beyond: Investigations into the Potential of Glutamatergic Agents to Treat Depression". Drugs. 77 (4): 381–401. doi:10.1007/s40265-017-0702-8. PMC 5342919. PMID 28194724.
  50. [50]
    Zorumski CF, Nagele P, Mennerick S, Conway CR (2015). "Treatment-Resistant Major Depression: Rationale for NMDA Receptors as Targets and Nitrous Oxide as Therapy". Frontiers in Psychiatry. 6: 172. doi:10.3389/fpsyt.2015.00172. PMC 4673867. PMID 26696909.
  51. [51]
    Chen C, Wang Z, Zhang Z, Liu X, Kang SS, Zhang Y, Ye K (January 2018). "The prodrug of 7,8-dihydroxyflavone development and therapeutic efficacy for treating Alzheimer's disease". Proceedings of the National Academy of Sciences of the United States of America. 115 (3): 578–583. Bibcode:2018PNAS..115..578C. doi:10.1073/pnas.1718683115. PMC 5777001. PMID 29295929.
  52. [52]
    Zeng Y, Wang X, Wang Q, Liu S, Hu X, McClintock SM (November 2013). "Small molecules activating TrkB receptor for treating a variety of CNS disorders". CNS & Neurological Disorders Drug Targets. 12 (7): 1066–77. doi:10.2174/18715273113129990089. PMID 23844685.
  53. [53]
    Zhang JC, Yao W, Hashimoto K (2016). "Brain-derived Neurotrophic Factor (BDNF)-TrkB Signaling in Inflammation-related Depression and Potential Therapeutic Targets". Current Neuropharmacology. 14 (7): 721–31. doi:10.2174/1570159X14666160119094646. PMC 5050398. PMID 26786147.
  54. [54]
    Liu C, Chan CB, Ye K (2016). "7,8-dihydroxyflavone, a small molecular TrkB agonist, is useful for treating various BDNF-implicated human disorders". Translational Neurodegeneration. 5: 2. doi:10.1186/s40035-015-0048-7. PMC 4702337. PMID 26740873.
  55. [55]
    Liu X, Chan CB, Jang SW, Pradoldej S, Huang J, He K, Phun LH, France S, Xiao G, Jia Y, Luo HR, Ye K (December 2010). "A synthetic 7,8-dihydroxyflavone derivative promotes neurogenesis and exhibits potent antidepressant effect". Journal of Medicinal Chemistry. 53 (23): 8274–86. doi:10.1021/jm101206p. PMC 3150605. PMID 21073191.
  56. [56]
    Zhang JC, Wu J, Fujita Y, Yao W, Ren Q, Yang C, Li SX, Shirayama Y, Hashimoto K (October 2014). "Antidepressant effects of TrkB ligands on depression-like behavior and dendritic changes in mice after inflammation". The International Journal of Neuropsychopharmacology. 18 (4). doi:10.1093/ijnp/pyu077. PMC 4360225. PMID 25628381.
  57. [57]
    Zhang JC, Yao W, Dong C, Yang C, Ren Q, Ma M, Han M, Hashimoto K (December 2015). "Comparison of ketamine, 7,8-dihydroxyflavone, and ANA-12 antidepressant effects in the social defeat stress model of depression". Psychopharmacology. 232 (23): 4325–35. doi:10.1007/s00213-015-4062-3. PMID 26337614. S2CID 15076700.
  58. [58]
    Chang HA, Wang YH, Tung CS, Yeh CB, Liu YP (September 2016). "7,8-Dihydroxyflavone, a Tropomyosin-Kinase Related Receptor B Agonist, Produces Fast-Onset Antidepressant-Like Effects in Rats Exposed to Chronic Mild Stress". Psychiatry Investigation. 13 (5): 531–540. doi:10.4306/pi.2016.13.5.531. PMC 5067348. PMID 27757132.
  59. [59]
    Zhang MW, Zhang SF, Li ZH, Han F (December 2016). "7,8-Dihydroxyflavone reverses the depressive symptoms in mouse chronic mild stress". Neuroscience Letters. 635: 33–38. doi:10.1016/j.neulet.2016.10.035. PMID 27773794. S2CID 157620.

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