List of investigational antidepressants
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. Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses. All drugs listed are specifically under development for major depressive disorder (MDD) or treatment-resistant depression (TRD) unless noted otherwise.
Glutamatergics
NMDA receptor modulators
- 4-Chlorokynurenine (AV-101) – NMDA receptor glycine site antagonist[1]
- AGN-241751 – NMDA receptor modulator[2][3]
- Apimostinel (NRX-1074) – NMDA receptor glycine site partial agonist[4]
- Arketamine (PCN-101, HR-071603) – unknown mechanism of action, indirect AMPA receptor activator[5][6]
- Dextromethadone (REL-1017) – NMDA receptor antagonist open channel blocker[7]
- EVT-101 (ENS-101) – NR2B antagonist[8]
- Ketamine (Ketalar) – non-competitive NMDA receptor antagonist[9]
- Rislenemdaz (CERC-301, MK-0657) – NMDA receptor subunit 2B (NR2B) antagonist[10]
Others
- Basimglurant (RG-7090) – mGluR5 negative allosteric modulator[11][12][13]
Monoaminergics
Monoamine reuptake inhibitors
- AN-788 (NSD-788) – serotonin–dopamine reuptake inhibitor (SDRI)[14]
- Ansofaxine (LY03005, LPM570065) – serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI)[15]
- PDC-1421 (BLI-1005) – norepinephrine reuptake inhibitor (NRI)[16]
Monoamine reuptake inhibitors and receptor modulators
- MIN-117 (WF-516) – SDRI, 5-HT1A receptor antagonist, 5-HT2A, α1A-adrenergic, and α1B-adrenergic receptor ligand[17]
- TGBA01AD (FKB01MD) – serotonin reuptake inhibitor (SRI), 5-HT1A and 5-HT1D receptor agonist, and 5-HT2 receptor antagonist[18]
Monoamine receptor modulators
- Gepirone (TGFK07AD; Travivo) – 5-HT1A receptor partial agonist[19]
- Pimavanserin (Nuplazid; ACP-103; BVF-048) – 5-HT2A receptor antagonist[20]
- Psilocybin – 5-HT2A receptor partial agonist[21]
Atypical antipsychotics
- Brilaroxazine (RP-5063, RP-5000) – AA – specifically under development for the treatment of MDD and depressive episodes in bipolar disorder[22]
- Lumateperone (ITI-007) – AA – specifically under development for the treatment of depressive episodes in bipolar disorder[23]
Others
- Ademetionine (SAMe; MSI-190, MSI-195, Strada) – cofactor in monoamine neurotransmitter biosynthesis – specifically under development in the United States and Europe for the adjunctive treatment of MDD[24]
Neurosteroids
GABAA receptor positive modulators
- Ganaxolone (CCD-1042) – GABAA receptor positive allosteric modulator – specifically under development for the treatment of postpartum depression[25]
- Zuranolone (SAGE-217) – GABAA receptor positive allosteric modulator – specifically under development for the treatment of both MDD and postpartum depression[26]
Others
- 3β-Methoxypregnenolone (MAP-4343) – selective microtubule-associated protein 2 (MAP2) stimulant[27]
- PH-10 – vomeropherine (precise mechanism of action unknown/undisclosed)[28]
Opioidergics
κ-Opioid receptor antagonists
- Aticaprant (JNJ-67953964, CERC-501, LY-2456302) – κ-opioid receptor antagonist[29][30]
- BTRX-335140 (BTRX-140) – selective k-opioid receptor antagonist[31][32]
- Buprenorphine/samidorphan (ALKS-5461) – κ-opioid receptor antagonist[33]
Others
- BTRX-246040 (LY-2940094) – nociceptin receptor antagonist[34]
Others
- Hydroxynorketamine ((2R,6R)-HNK) – metabolite of ketamine which may be involved in ketamine's antidepressant-like effects in mice[5][35]
- JNJ-39393406 – α7 nicotinic acetylcholine receptor positive allosteric modulator[36]
- JNJ-54175446 – P2RX7 purinoceptor antagonist[37]
- JNJ-61393215 – (JNJ-3215, JNJ-61393215; Orexin-1) Orexin receptor antagonists(type 1)[38][39]
- NNI-351 – DYRK1A inhibitor/"nerve growth factor stimulant"[40]
- NSI-189 – hippocampal neurotrophic agent (precise mechanism of action unknown)[41]
- NV-5138 – sestrin2 modulator and consequent mammalian target of rapamycin complex 1 (mTORC1) activator[42][43][44]
- OnabotulinumtoxinA (botulinum toxin A, Botox) – acetylcholine release inhibitor – specifically under development for the treatment of MDD in women as a local injection to paralyze facial muscles[45]
- Pramipexole (CTC-501, CTC-413) – Dopamine D2 and D3 receptor agonists.[46][47]
- Seltorexant (MIN-202, JNJ-42847922, JNJ-922) – OX2 receptor antagonist[48]
- Sirukumab (CNTO-136) – monoclonal antibody against interleukin-6[49]
- SUVN-911 – α4β2 nicotinic acetylcholine receptor antagonist or negative allosteric modulator[50]
- TS-121 – vasopressin 1B receptor antagonist[51]
Mixed
- Tramadol (ETS6103; Viotra) – μ-opioid receptor agonist, serotonin–norepinephrine reuptake inhibitor (SNRI) and possible serotonin releasing agent (SRA), 5-HT2C receptor antagonist, and other actions[52][53][54]
Combinations
- Bupropion/dextromethorphan (AXS-05) – σ1 receptor agonist, SNRI, non-competitive nicotinic acetylcholine receptor antagonist, uncompetitive NMDA receptor antagonist, and other actions[55]
- Cycloserine/lurasidone (NRX-101; Cyclurad) – NMDA receptor glycine site partial agonist and AA combination – specifically under development for the treatment of depressive episodes in bipolar disorder[56]
- Dextromethorphan/quinidine (AVP-786/AVP-923) – σ1 receptor agonist, SNRI, uncompetitive NMDA receptor antagonist, and other actions[57]
Not under development
The following drugs are currently of investigational interest as potential antidepressants but are not formally under clinical development for approval at this time:
- 7,8-Dihydroxyflavone (7,8-DHF) – TrkB agonist[58][59][60][61][62][63][64][65]
- Minocycline – microglia inhibitor and other actions; a 2018 systematic review and meta-analysis reported that the overall antidepressant effect size of minocycline compared to placebo was -0.78 (95% CI: -0.4 to -1.33, P=0.005), indicative of a large and statistically significant antidepressant effect[66][67]
- Nitrous oxide – NMDA receptor antagonist and other actions[68][13][69]
- Pramipexole – partial or full agonist of the D2, D3, and D4 receptors[70]
- R13 – an orally active prodrug of 7,8-DHF with improved pharmacokinetics[71]
- LSD[72]
References
- "AV 101". adisinsight.springer.com. Retrieved 7 May 2017.
- "AGN-241751 - Allergan". adisinsight.springer.com. Retrieved 28 August 2018.
- "Allergan Exercises Option to Acquire Compound from Aptinyx Discovery Platform Under Ongoing Research Collaboration". www.prnewswire.com. Retrieved 28 August 2018.
- "Apimostinel". adisinsight.springer.com. Retrieved 7 May 2017.
- Hashimoto, Kenji (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. ISSN 1323-1316. PMC 6851782. PMID 31215725.
- https://adisinsight.springer.com/drugs/800056158
- "Dextromethadone - Relmada Therapeutics". adisinsight.springer.com. Retrieved 10 November 2018.
- "EVT 101". adisinsight.springer.com. Retrieved 7 May 2017.
- "Ketamine intranasal - Vyera Pharmaceuticals". adisinsight.springer.com. Retrieved 7 May 2017.
- "CERC 301". adisinsight.springer.com. Retrieved 7 May 2017.
- "Basimglurant". adisinsight.springer.com. Retrieved 7 May 2017.
- Machado-Vieira R, Henter ID, Zarate CA (May 2017). "New targets for rapid antidepressant action". Progress in Neurobiology. 152: 21–37. doi:10.1016/j.pneurobio.2015.12.001. PMC 4919246. PMID 26724279.
- 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.
- "AN 788". adisinsight.springer.com. Retrieved 7 May 2017.
- "LY 03005". adisinsight.springer.com. Retrieved 7 May 2017.
- "PDC-1421". adisinsight.springer.com. Retrieved 24 March 2018.
- "MIN 117". adisinsight.springer.com. Retrieved 7 May 2017.
- "FKB 01MD". adisinsight.springer.com. Retrieved 7 May 2017.
- "Gepirone ER". adisinsight.springer.com. Retrieved 7 May 2017.
- "Pimavanserin". adisinsight.springer.com. Retrieved 25 September 2017.
- "Psilocybin". adisinsight.springer.com. Retrieved 26 October 2018.
- "RP 5063". adisinsight.springer.com. Retrieved 7 May 2017.
- "Lumateperone". adisinsight.springer.com. Retrieved 7 May 2017.
- "Ademetionine". adisinsight.springer.com. Retrieved 7 May 2017.
- "Ganaxolone". adisinsight.springer.com. Retrieved 24 March 2018.
- "SAGE 217". adisinsight.springer.com. Retrieved 9 February 2018.
- "Pregnenolone methyl ether". adisinsight.springer.com. Retrieved 7 May 2017.
- "PH 10 nasal spray". adisinsight.springer.com. Retrieved 7 May 2017.
- "Aticaprant". adisinsight.springer.com. Retrieved 11 November 2019.
- https://adisinsight.springer.com/drugs/800052341
- "BlackThorn Therapeutics Advances Phase 2 Clinical Development for Selective KOR Antagonist, BTRX-140, in Neuropsychiatric Disorders". BlackThorn Therapeutics. Retrieved 2020-01-25.
- "BTRX 335140 - AdisInsight". adisinsight.springer.com. Retrieved 2020-01-25.
- "Buprenorphine/samidorphan". adisinsight.springer.com. Retrieved 7 May 2017.
- "BTRX-246040". adisinsight.springer.com. Retrieved 24 March 2018.
- 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. doi:10.1038/nature17998. PMC 4922311. PMID 27144355. Lay summary – ScienceDaily.
- "JNJ 39393406". adisinsight.springer.com. Retrieved 7 May 2017.
- "JNJ-54175446". adisinsight.springer.com. Retrieved 24 March 2018.
- "JNJ 61393215 - AdisInsight". adisinsight.springer.com. Retrieved 2020-01-25.
- "A Study of JNJ-61393215 in the Treatment of Depression - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2020-01-25.
- "Research programme: psychiatric and neurological disorders therapeutics - Neuronascent". adisinsight.springer.com. Retrieved 7 May 2017.
- "NSI 189". adisinsight.springer.com. Retrieved 7 May 2017.
- "NV 5138". adisinsight.springer.com. Retrieved 7 November 2018.
- 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.
- 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.
- "Botulinum toxin A injectable - Allergan". adisinsight.springer.com. Retrieved 7 May 2017.
- "Product Discovery and Development". Chase Therapeutics. Retrieved 2020-01-25.
- "Pramipexole - Chase Therapeutics - AdisInsight". adisinsight.springer.com. Retrieved 2020-01-25.
- "JNJ 42847922". adisinsight.springer.com. Retrieved 7 May 2017.
- "Sirukumab". adisinsight.springer.com. Retrieved 7 May 2017.
- "SUVN-911". adisinsight.springer.com. Retrieved 24 March 2018.
- "TS 121". adisinsight.springer.com. Retrieved 7 May 2017.
- "Tramadol controlled release - e-Therapeutics". adisinsight.springer.com. Retrieved 7 May 2017.
- "Another depression drug flops as e-Therapeutics tallies PhIIb data - FierceBiotech". www.fiercebiotech.com. Retrieved 28 August 2018.
- "E-Therapeutics defends PhIIb fail, claiming drug has 'pretty much' the hoped-for profile - FierceBiotech". www.fiercebiotech.com. Retrieved 28 August 2018.
- "Bupropion/dextromethorphan - Axsome Therapeutics". adisinsight.springer.com. Retrieved 7 May 2017.
- "Cycloserine/lurasidone - NeuroRx". adisinsight.springer.com. Retrieved 7 May 2017.
- "Deudextromethorphan". adisinsight.springer.com. Retrieved 7 May 2017.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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. doi:10.1038/s41598-017-01590-x. PMC 5431207. PMID 28469132.
- 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.
- 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.
- Harrison, Pam (April 7, 2016). "Parkinson's Drug Highly Effective for Resistant Depression". www.medscape.com. WebMD. Retrieved 2018-02-12.
- 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. doi:10.1073/pnas.1718683115. PMC 5777001. PMID 29295929.
- Dos Santos RG, Osório FL, Crippa JA, Riba J, Zuardi AW, Hallak JE (June 2016). "Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years". Therapeutic Advances in Psychopharmacology. 6 (3): 193–213. doi:10.1177/2045125316638008. PMC 4910400. PMID 27354908.
Further reading
- Ionescu DF, Papakostas GI (March 2017). "Experimental medication treatment approaches for depression". Translational Psychiatry. 7 (3): e1068. doi:10.1038/tp.2017.33. PMC 5416676. PMID 28323287.
- Garay RP, Zarate CA, Charpeaud T, Citrome L, Correll CU, Hameg A, Llorca PM (June 2017). "Investigational drugs in recent clinical trials for treatment-resistant depression". Expert Review of Neurotherapeutics. 17 (6): 593–609. doi:10.1080/14737175.2017.1283217. PMC 5418088. PMID 28092469.
- Dhir A (January 2017). "Investigational drugs for treating major depressive disorder". Expert Opinion on Investigational Drugs. 26 (1): 9–24. doi:10.1080/13543784.2017.1267727. PMID 27960559.
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