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) and/or treatment-resistant depression (TRD) unless noted otherwise. Other forms of depression may include bipolar depression and postpartum depression.

Glutamatergics

NMDA receptor modulators

AMPA receptor modulators

Monoaminergics

Monoamine reuptake inhibitors

Monoamine reuptake inhibitors and receptor modulators

  • Hypidone (YL-0919) – SRI, 5-HT1A receptor partial agonist, and 5-HT6 receptor agonist
  • TGBA01AD (FKB01MD) – serotonin reuptake inhibitor (SRI), 5-HT1A and 5-HT1D receptor agonist, and 5-HT2 receptor antagonist[10]
  • Vortioxetine (Trintellix) – SRI, 5-HT1A receptor agonist, 5-HT1B receptor partial agonist, 5-HT1D, 5-HT3, and 5-HT7 receptor antagonist – approved for MDD, under development for bipolar depression

Monoamine releasing agents

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[11][12]
  • Gepirone (TGFK07AD; Travivo) – 5-HT1A receptor partial agonist[13]
  • Pramipexole (CTC-501, CTC-413) – D2, D3, and D4 receptor agonist[14][15]
  • Psilocybin – 5-HT2A receptor agonist[16]

Atypical antipsychotics

  • Brilaroxazine (RP-5063, RP-5000) – AA – specifically under development for the treatment of MDD[17]
  • Cariprazine (Reagila, Vraylar) – AA – approved for bipolar depression, under development for MDD
  • Lumateperone (ITI-007) – AA – specifically under development for the treatment of MDD and bipolar depression[18]
  • 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[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

  • PRAX-114 – GABAA receptor positive allosteric modulator
  • Zuranolone (SAGE-217) – GABAA receptor positive allosteric modulator – specifically under development for the treatment of MDD and postpartum depression[21]

Others

Opioidergics

κ-Opioid receptor antagonists

Nociceptin receptor antagonists

Cholinergics

Muscarinic acetylcholine receptor modulators

Nicotinic acetylcholine receptor modulators

  • JNJ-39393406 – α7 nicotinic acetylcholine receptor positive allosteric modulator[30]

Others

Orexin receptor antagonists

Others

  • BI-1358894 – TRPC4 and TRPC5 inhibitor
  • Crisdesalazine (AAD-2004) – MPGES-1 inhibitor
  • Erteberel – selective ERβ receptor agonist
  • JNJ-54175446 – P2RX7 purinoceptor antagonist[35]
  • NSI-189 – hippocampal neurotrophic agent (precise mechanism of action unknown)[36]
  • NV-5138 – sestrin2 modulator and consequent mammalian target of rapamycin complex 1 (mTORC1) activator[37][38][39]
  • SNG-12 – undefined mechanism of action
  • TS-121 – vasopressin 1B receptor antagonist[40]
  • WIP-DF17 – undefined mechanism of action

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

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  2. ↑ "Apimostinel". adisinsight.springer.com. Retrieved 7 May 2017.
  3. 1 2 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.
  4. ↑ https://adisinsight.springer.com/drugs/800056158
  5. ↑ "Dextromethadone - Relmada Therapeutics". adisinsight.springer.com. Retrieved 10 November 2018.
  6. ↑ "Ketamine intranasal - Vyera Pharmaceuticals". adisinsight.springer.com. Retrieved 7 May 2017.
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  8. ↑ "PDC-1421". adisinsight.springer.com. Retrieved 24 March 2018.
  9. ↑ "LY 03005". adisinsight.springer.com. Retrieved 7 May 2017.
  10. ↑ "FKB 01MD". adisinsight.springer.com. Retrieved 7 May 2017.
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