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]
- Esketamine (JNJ-54135419, Ketanest S) – non-competitive NMDA receptor antagonist[5]
- EVT-101 (ENS-101) – NR2B antagonist[6]
- EVT-103 (ENS-103) – NR2B antagonist[7]
- Ketamine (Ketalar) – non-competitive NMDA receptor antagonist[8]
- Rapastinel (GLYX-13) – NMDA receptor glycine site partial agonist[9]
- Rislenemdaz (CERC-301, MK-0657) – NMDA receptor subunit 2B (NR2B) antagonist[10]
Others
- Basimglurant (RG-7090) – mGluR5 negative allosteric modulator[11][12][13]
- Tulrampator (S-47445, CX-1632) – AMPA receptor positive allosteric modulator[14]
Monoaminergics
Monoamine reuptake inhibitors
- AN-788 (NSD-788) – serotonin–dopamine reuptake inhibitor (SDRI)[15]
- Ansofaxine (LY03005, LPM570065) – serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI)[16]
- PDC-1421 (BLI-1005) – norepinephrine reuptake inhibitor (NRI)[17]
Monoamine reuptake inhibitors and receptor modulators
- MIN-117 (WF-516) – SDRI, 5-HT1A receptor antagonist, 5-HT2A, α1A-adrenergic, and α1B-adrenergic receptor ligand[18]
- TGBA01AD (FKB01MD) – serotonin reuptake inhibitor (SRI), 5-HT1A and 5-HT1D receptor agonist, and 5-HT2 receptor antagonist[19]
Monoamine receptor modulators
- Gepirone (TGFK07AD; Travivo) – 5-HT1A receptor partial agonist[20]
- Pimavanserin (Nuplazid; ACP-103; BVF-048) – 5-HT2A receptor antagonist[21]
Atypical antipsychotics
- Aripiprazole/sertraline (ASC-01) – atypical antipsychotic (AA) and selective serotonin reuptake inhibitor (SSRI) combination[22]
- Cariprazine (Vraylar) – AA – specifically under development for the adjunctive treatment of MDD and as a monotherapy for depressive episodes in bipolar disorder[23]
- Lumateperone (ITI-007) – AA – specifically under development for the treatment of depressive episodes in bipolar disorder[24]
- Lurasidone (Latuda) – AA – specifically under development for the treatment of MDD[25]
- RP-5063 (RP-5000) – AA – specifically under development for the treatment of MDD and depressive episodes in bipolar disorder[26]
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[27]
Neurosteroids
GABAA receptor positive modulators
- Brexanolone (allopregnanolone; SAGE-547) – GABAA receptor positive allosteric modulator – specifically under development for the treatment of postpartum depression[28]
- Ganaxolone (CCD-1042) – GABAA receptor positive allosteric modulator – specifically under development for the treatment of postpartum depression[29]
- SAGE-217 – GABAA receptor positive allosteric modulator – specifically under development for the treatment of both MDD and postpartum depression[30]
Others
- 3β-Methoxypregnenolone (MAP-4343) – selective microtubule-associated protein 2 (MAP2) stimulant[31]
- PH-10 – vomeropherine (precise mechanism of action unknown/undisclosed)[32]
Opioidergics
κ-Opioid receptor antagonists
- Buprenorphine/samidorphan (ALKS-5461) – κ-opioid receptor antagonist[33]
- CERC-501 (LY-2456302) – κ-opioid receptor antagonist[34]
Others
- BTRX-246040 (LY-2940094) – nociceptin receptor antagonist[35]
Others
- JNJ-39393406 – α7 nicotinic acetylcholine receptor positive allosteric modulator[36]
- JNJ-54175446 – P2RX7 purinoceptor antagonist[37]
- NNI-351 – DYRK1A inhibitor/"nerve growth factor stimulant"[38]
- NSI-189 – hippocampal neurotrophic agent (precise mechanism of action unknown)[39]
- NV-5138 – sestrin2 modulator and consequent mammalian target of rapamycin complex 1 (mTORC1) activator[40][41]
- 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[42]
- Seltorexant (MIN-202, JNJ-42847922, JNJ-922) – OX2 receptor antagonist[43]
- Sirukumab (CNTO-136) – monoclonal antibody against interleukin-6[44]
- SUVN-911 – α4β2 nicotinic acetylcholine receptor antagonist or negative allosteric modulator[45]
- TS-121 – vasopressin 1B receptor antagonist[46]
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[47][48][49]
Combinations
- Bupropion/dextromethorphan (AXS-05) – σ1 receptor agonist, SNRI, non-competitive nicotinic acetylcholine receptor antagonist, uncompetitive NMDA receptor antagonist, and other actions[50]
- Cycloserine/lurasidone (Cyclurad) – NMDA receptor glycine site partial agonist and AA combination – specifically under development for the treatment of depressive episodes in bipolar disorder[51]
- Dextromethorphan/quinidine (AVP-786/AVP-923) – σ1 receptor agonist, SNRI, uncompetitive NMDA receptor antagonist, and other actions[52]
Not under development
The following drugs are currently of major 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[53][54][55][56][57][58][59][60]
- Hydroxynorketamine ((2R,6R)-HNK) – metabolite of ketamine which may be involved in ketamine's antidepressant-like effects in mice[61][62]
- 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[63][64]
- Nitrous oxide – NMDA receptor antagonist and other actions[65][13][66]
- Pramipexole – partial or full agonist of the D2, D3, and D4 receptors[67]
- R13 – an orally active prodrug of 7,8-DHF with improved pharmacokinetics[68]
- MIF-1 – (MSH release–inhibitor) [69]
See also
References
- ↑ "AV 101 - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "Research programme: NMDA receptor modulators - Allergan - AdisInsight". 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". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "Esketamine - Johnson & Johnson - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "EVT 101 - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "EVT 103 - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "Ketamine intranasal - Vyera Pharmaceuticals - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "Rapastinel - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "CERC 301 - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "Basimglurant - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ Machado-Vieira R, Henter ID, Zarate CA (2017). "New targets for rapid antidepressant action". Prog. Neurobiol. 152: 21–37. doi:10.1016/j.pneurobio.2015.12.001. PMID 26724279.
- 1 2 Lener MS, Kadriu B, Zarate CA (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. PMID 28194724.
- ↑ "Tulrampator - AdisInsight". adisinsight.springer.com. Retrieved 31 May 2017.
- ↑ "AN 788 - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "LY 03005 - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "PDC-1421 - AdisInsight". adisinsight.springer.com. Retrieved 24 March 2018.
- ↑ "MIN 117 - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "FKB 01MD - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "Gepirone ER - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "Pimavanserin - AdisInsight". adisinsight.springer.com. Retrieved 25 September 2017.
- ↑ "Aripiprazole/sertraline - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "Cariprazine - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "Lumateperone - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "Lurasidone - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "RP 5063 - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "Ademetionine - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "Brexanolone - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "Ganaxolone - AdisInsight". adisinsight.springer.com. Retrieved 24 March 2018.
- ↑ "SAGE 217 - AdisInsight". adisinsight.springer.com. Retrieved 9 February 2018.
- ↑ "Pregnenolone methyl ether - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "PH 10 nasal spray - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "Buprenorphine/samidorphan - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "CERC 501 - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "BTRX-246040 - AdisInsight". adisinsight.springer.com. Retrieved 24 March 2018.
- ↑ "JNJ 39393406 - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "JNJ-54175446 - AdisInsight". adisinsight.springer.com. Retrieved 24 March 2018.
- ↑ "Research programme: psychiatric and neurological disorders therapeutics - Neuronascent - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "NSI 189 - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ Duman RS (2018). "Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide". F1000Res. 7. doi:10.12688/f1000research.14344.1. PMC 5968361. PMID 29899972.
- ↑ Duman, R., Kato, T., Liu, R. J., Duman, C., Terwilliger, R., Vlasuk, G., ... & Sajah, E. (2017, November). Sestrin 2 Modulator NV-5138 Shows Ketamine-Like Rapid Antidepressant Effects via Direct Activation of mTORC1 Signaling. In Neuropsychopharmacology (Vol. 43, pp. S195-S195). Macmillan Building, 4 Crinan St, London N1 9Xw, England: Nature Publishing Group. https://www.nature.com/articles/npp2017264.pdf
- ↑ "Botulinum toxin A injectable - Allergan - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "JNJ 42847922 - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "Sirukumab - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "SUVN-911 - AdisInsight". adisinsight.springer.com. Retrieved 24 March 2018.
- ↑ "TS 121 - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "Tramadol controlled release - e-Therapeutics - AdisInsight". 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". adisinsight.springer.com. Retrieved 7 May 2017.
- ↑ "Cycloserine/lurasidone - NeuroRx - AdisInsight". adisinsight.springer.com. Retrieved 7 May 2017.
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- ↑ 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 Neurol Disord 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". Curr Neuropharmacol. 14 (7): 721–31. 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". Transl Neurodegener. 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". J. Med. Chem. 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". Int. J. Neuropsychopharmacol. 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 Investig. 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". Neurosci. Lett. 635: 33–38. doi:10.1016/j.neulet.2016.10.035. PMID 27773794.
- ↑ Zanos, Panos; Moaddel, Ruin; Morris, Patrick J.; Georgiou, Polymnia; Fischell, Jonathan; Elmer, Greg I.; Alkondon, Manickavasagom; Yuan, Peixiong; Pribut, Heather J.; Singh, Nagendra S.; Dossou, Katina S. S.; Fang, Yuhong; Huang, Xi-Ping; Mayo, Cheryl L.; Wainer, Irving W.; Albuquerque, Edson X.; Thompson, Scott M.; Thomas, Craig J.; Zarate Jr, Carlos A.; Gould, Todd D. (2016). "NMDAR inhibition-independent antidepressant actions of ketamine metabolites". Nature. 533: 481–486. doi:10.1038/nature17998. ISSN 0028-0836. PMC 4922311. PMID 27144355.
- ↑ NIH/National Institute of Mental Health. (2016, May 4). Ketamine lifts depression via a byproduct of its metabolism: Team finds rapid-acting, non-addicting agent in mouse study. ScienceDaily. Retrieved May 7, 2016
- ↑ Rosenblat JD, McIntyre RS (2018). "Efficacy and tolerability of minocycline for depression: A systematic review and meta-analysis of clinical trials". J Affect Disord. 227: 219–225. doi:10.1016/j.jad.2017.10.042. PMID 29102836.
- ↑ Cohen IV, Makunts T, Atayee R, Abagyan R (2017). "Population scale data reveals the antidepressant effects of ketamine and other therapeutics approved for non-psychiatric indications". Sci Rep. 7 (1): 1450. doi:10.1038/s41598-017-01590-x. PMC 5431207. PMID 28469132.
- ↑ Nagele P, Zorumski CF, Conway C (2018). "Exploring Nitrous Oxide as Treatment of Mood Disorders: Basic Concepts". J Clin Psychopharmacol. doi:10.1097/JCP.0000000000000837. 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". Front 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". Proc. Natl. Acad. Sci. U.S.A. 115 (3): 578–583. doi:10.1073/pnas.1718683115. PMID 29295929.
- ↑ "MIF-1 - AdisInsight". adisinsight.springer.com. Retrieved 23 Aug 2002.
Further reading
- Ionescu DF, Papakostas GI (2017). "Experimental medication treatment approaches for depression". Transl Psychiatry. 7 (3): e1068. doi:10.1038/tp.2017.33. PMID 28323287.
- Garay RP, Zarate CA, Charpeaud T, Citrome L, Correll CU, Hameg A, Llorca PM (2017). "Investigational drugs in recent clinical trials for treatment-resistant depression". Expert Rev Neurother. 17 (6): 593–609. doi:10.1080/14737175.2017.1283217. PMID 28092469.
- Dhir A (2017). "Investigational drugs for treating major depressive disorder". Expert Opin Investig Drugs. 26 (1): 9–24. doi:10.1080/13543784.2017.1267727. PMID 27960559.
External links
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