List of investigational antidepressants
This is a list of investigational antidepressants, or
bipolar depression and postpartum depression
.
Drugs that have been investigated but are not currently in development as antidepressants are given in italic.
Glutamatergics
NMDA receptor modulators
- glycine site antagonist[1]
- modulator[2]
- Arketamine (PCN-101, HR-071603) – unknown mechanism of action, indirect AMPA receptor activator[3][4]
- Esketamine (Esketamine DPI, Falkieri, PG061) – non-competitive NMDA receptor antagonist – approved for TRD, specifically under development for bipolar depression and "depressive disorders" [1]
- Esmethadone (dextromethadone; REL-1017) – NMDA receptor antagonist open channel blocker[5]
- Ketamine (PMI-100, PMI-150, R-107, SHX-001, SLS-002; TUR-002) – non-competitive NMDA receptor antagonist.[6][2][3][4]
- Rislenemdaz (ALTO-202) – NMDA receptor NR2B antagonist. In development for Depression and PTSD by ALTO Neuroscience.[7]
AMPA receptor modulators
- positive allosteric modulator [5]
Monoaminergics
Monoamine reuptake inhibitors
- OPC-64005 – serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI) [6]
- PDC-1421 (BLI-1005) – norepinephrine reuptake inhibitor (NRI)[10]
Monoamine reuptake inhibitors and receptor modulators
- Hypidone (YL-0919) – SRI, 5-HT1A receptor partial agonist, and 5-HT6 receptor agonist [7]
- TGBA01AD (FKB01MD) – serotonin reuptake inhibitor (SRI), 5-HT1A and 5-HT1D receptor agonist, and 5-HT2 receptor antagonist[11]
Monoamine releasing agents
- Midomafetamine (MDMA; ecstasy) – serotonin–norepinephrine–dopamine releasing agent (SNDRA) [8]
Monoamine receptor modulators
- 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[12][13]
- Psilocybin – 5-HT2A receptor agonist[16][9]
Atypical antipsychotics
- Brilaroxazine (RP-5063, RP-5000) – AA – specifically under development for the treatment of MDD[17]
- Lumateperone (ITI-007, Caplyta) – AA – specifically under development for the treatment of MDD and bipolar.[18] Has been approved to treat BP 1 and BP 2 disorder under the brand name Caplyta.[10]
- Lurasidone (Latuda) – AA – specifically under development for the treatment of MDD [11]
- Pimavanserin (Nuplazid; ACP-103; BVF-048) – 5-HT2A receptor antagonist – specifically under development for the treatment of MDD[19]
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[20]
GABAergics and neurosteroids
GABAA receptor positive modulators
- Zuranolone (SAGE-217) – GABAA receptor positive allosteric modulator – specifically under development for the treatment of MDD and postpartum depression[21]
Others
- 3β-Methoxypregnenolone (MAP-4343) – selective microtubule-associated protein 2 (MAP2) stimulant[22]
- vomeropherine (precise mechanism of action unknown/undisclosed)[23]
Opioidergics
κ-Opioid receptor antagonists
- Aticaprant (JNJ-67953964, CERC-501, LY-2456302) – selective κ-opioid receptor antagonist[24]
- Buprenorphine/samidorphan (ALKS-5461) – κ-opioid receptor antagonist and μ-opioid receptor antagonist[25]
- CVL-354 – selective κ-opioid receptor antagonist[26]
- Navacaprant (BTRX-335140; BTRX-140) – selective k-opioid receptor antagonist[27][28]
Nociceptin receptor antagonists
- BTRX-246040 (LY-2940094) – nociceptin receptor antagonist[29]
Cholinergics
Muscarinic acetylcholine receptor modulators
- muscarinic acetylcholine receptor antagonist [12]
Others
- release inhibitor – specifically under development for the treatment of MDD in women as a local injection to paralyze facial muscles[30]
Orexin receptor antagonists
- Seltorexant (MIN-202, JNJ-42847922, JNJ-922) – OX2 receptor antagonist[33]
Others
- Crisdesalazine (AAD-2004) – MPGES-1 inhibitor [14]
- ERβ receptor agonist [15]
- JNJ-54175446 – P2RX7 purinoceptor antagonist[34]
- NSI-189 – hippocampal neurotrophic agent (precise mechanism of action unknown)[35]
- SNG-12 – undefined mechanism of action [16]
- vasopressin 1B receptor antagonist[39]
- WIP-DF17 – undefined mechanism of action [17]
- XEN1101 – KCNQ2/3 channel opener [40][41]
- Casopitant – NK1 receptor antagonist[42]
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[43][44][45]
Combinations
- serotonin precursor and aromatic L-amino acid decarboxylase inhibitor [18]
- Cycloserine/lurasidone (NRX-101; Cyclurad) – NMDA receptor glycine site partial agonist and AA combination – specifically under development for the treatment of bipolar depression[46]
- Deudextromethorphan/quinidine (AVP-786, CTP-786) – σ1 receptor agonist, SRI, uncompetitive NMDA receptor antagonist, and other actions[47]
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:
- Hydroxynorketamine ((2R,6R)-HNK) – metabolite of ketamine which may be involved in ketamine's antidepressant-like effects in mice[3][48]
- Nitrous oxide – NMDA receptor antagonist and other actions[53][54][55]
- R13 – an orally active prodrug of tropoflavin with improved pharmacokinetics[56]
See also
- List of antidepressants
- List of investigational drugs
References
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- ^ "Ketamine intranasal - Vyera Pharmaceuticals". adisinsight.springer.com. Archived from the original on 24 September 2017. Retrieved 7 May 2017.
- ^ "CERC 301". adisinsight.springer.com. Retrieved 7 May 2017.
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- ^ "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.
- ^ "PDC-1421". adisinsight.springer.com. Retrieved 24 March 2018.
- ^ "FKB 01MD". adisinsight.springer.com. Retrieved 7 May 2017.
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- ^ "Pramipexole - Chase Therapeutics - AdisInsight". adisinsight.springer.com. Retrieved 2020-01-25.
- ^ "Product Discovery and Development". Chase Therapeutics. Retrieved 2020-01-25.
- ^ "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.
- ^ "Pimavanserin". adisinsight.springer.com. Retrieved 25 September 2017.
- ^ "Ademetionine". adisinsight.springer.com. Retrieved 7 May 2017.
- ^ "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 (JNJ-67953964, CERC-501, LY-2456302) - AdisInsight". adisinsight.springer.com. Retrieved 2022-08-29.
- ^ "Buprenorphine/samidorphan". adisinsight.springer.com. Retrieved 7 May 2017.
- ^ "CVL-354". adisinsight.springer.com. Retrieved 2 February 2023.
- ^ "BTRX 335140 - AdisInsight". adisinsight.springer.com. Retrieved 2020-01-25.
- ^ "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.
- ^ "BTRX-246040". adisinsight.springer.com. Retrieved 24 March 2018.
- ^ "Botulinum toxin A injectable - Allergan". adisinsight.springer.com. Retrieved 7 May 2017.
- ^ "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.
- ^ "JNJ 42847922". adisinsight.springer.com. Retrieved 7 May 2017.
- ^ "JNJ-54175446". adisinsight.springer.com. Retrieved 24 March 2018.
- ^ "NSI 189". adisinsight.springer.com. Retrieved 7 May 2017.
- ^ "NV 5138". adisinsight.springer.com. Retrieved 7 November 2018.
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- ^ "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. 15 February 2016. Retrieved 28 August 2018.
- ^ "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.
- ^ "Cycloserine/lurasidone - NeuroRx". adisinsight.springer.com. Retrieved 7 May 2017.
- ^ "Deudextromethorphan". adisinsight.springer.com. Retrieved 7 May 2017.
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Further reading
- Ionescu DF, Papakostas GI (March 2017). "Experimental medication treatment approaches for depression". Translational Psychiatry. 7 (3): e1068. 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. PMID 28092469.
- Dhir A (January 2017). "Investigational drugs for treating major depressive disorder". Expert Opinion on Investigational Drugs. 26 (1): 9–24. S2CID 45232796.