List of antipsychotics under development in 2024【Revised 2024.1.26】

Introduction

I’ll do as much research as I can about the antipsychotics in development in the list below, and I’ll write articles about them one by one. I would be happy if you think that innovative drugs will come in the future.

This article lists antipsychotics. In addition, I added drugs for negative and cognitive symptoms to the list.

I’ll investigate the study results, mechanism of action, efficacy, side effects, which stage of study (phase) it is in, and which company is developing it.

It seems that the clinical trial process in Japan takes about 0.5-1 years for Phase I, about 2 years for Phase II, and about 2-3 years for Phase III.

A drug is released about 1 year after the application, and it takes about 8 years in total from the start of the clinical trial.

Concerning drugs already released overseas, once a clinical trial for a drug begins in Japan, it takes at least 5 or 6 years before it is released.

However, for example, Pyridoxamine has been in clinical trial for about 10 years and is still in phase II. Some drugs may be substantially delayed or even withdrawn from trials.

Antipsychotics under Development

Receptor modulators (Five types)

①Monoamine receptor modulators

1. (marketed)Lumateperone (ITI-007, ITI-722) – atypical antipsychotic (D2 receptor partial agonist, 5-HT2A receptor antagonist, other actions)
2. (marketed)Latuda (lurasidone) – D2 and 5HT2A receptor antagonist, 5HT1A receptor partial agonist, 5HT7A receptor antagonist
3. Solian(Amisulpride,LB-102)– D2, D3 and 5HT7, 5HT2B receptor antagonist
4. Brilaroxazine (RP-5063, RP-5000; oxaripiprazole) – atypical antipsychotic (D2 receptor partial agonist, 5-HT2A receptor antagonist, other actions)
5. FKF-02SC (TGOF-02N) – atypical antipsychotic (D2 and 5-HT2A receptor antagonist, other actions)
6. Masupirdine (SUVN-502) – 5-HT6 receptor antagonist
7. Ralmitaront (RG-7906, RO-6889450) – TAAR1 agonist
8. Ulotaront (SEP-856, SEP-363856) – 5-HT1A receptor and TAAR1 agonist
9. Usmarapride – serotonin 5HT4A receptor partial agonist

②Glutamate receptor modulators

1. Pomaglumetad methionil (DB-103, LY-2140023, LY-2812223) – mGluR2 and mGluR3 agonist

③Acetylcholine receptor modulators

1. (marketed)KarXT (xanomeline/trospium) (Cobenfy)– combined M1 and M4 muscarinic acetylcholine receptor agonist and peripherally-selective muscarinic acetylcholine receptor antagonist
2. NBI-1117568(HTL16878) – M4 Muscarinic Acetylcholine Receptor Agonist
3. Emraclidine(CVL-231) – Positive Allosteric Modulator of M4 Receptor
4. ML-007 – M1 and M4 Muscarinic Acetylcholine Receptor Agonist

④Cannabinoid receptor modulators

1. Cannabidiol (CBD; GW-42003, GWP-42003, GWP-42003-P, ECP-012A; Arvisol, Epidiolex) – cannabinoid receptor modulator, antioxidant, other actions

⑤Other/mixed receptor modulators

1. Deudextromethorphan (d-DM; AVP-786, CTP-786) – σ1 receptor agonist, serotonin–norepinephrine reuptake inhibitor, uncompetitive NMDA receptor antagonist, muscarinic acetylcholine receptor agonist, other actions
2. TAK-041 – GPR139 receptor agonist
3. Olanzapine + Samidorphan (Lybalvi) – combination atypical antipsychotic (D2 and 5-HT2A receptor antagonist, other effects) + (mu opioid receptor antagonist)
4. CVN766 – Orexin receptor type 1 antagonist

(Four) Enzyme inhibitors

1. Luvadaxistat (TAK-831) – D-amino acid oxidase inhibitor
2. MK-8189 – phosphodiesterase 10A inhibitor
3. Osoresnontrine (BI-409306, SUB-166499) – phosphodiesterase 9A inhibitor
4. Sodium benzoate (SND-11, SND-12, SND-13, SND-14; Clozaben, NaBen) – D-amino acid oxidase inhibitor

(Two) Ion channel modulators

1. Evenamide (NW-3509; NW-3509A) – Nav1.3, Nav1.7, and Nav1.8 voltage-gated sodium channel blocker

Others

1. TS-134 (TS-1341) – undefined mechanism of action
2. HTL0041178 – GPR52 agonist
3. Kratom – Has shown antipsychotic-like effects on par with haloperidol

Drugs for Cognitive and Negative Symptoms

1. Roluperidone (CYR-101, MIN-101, MT-210) – 5-HT2A and σ2 receptor antagonist
2. BI425809 – glycine transporter 1 (GlyT1) inhibitor
3. RL-007 – Acetylcholine receptor modulator, GABAB receptor modulator, NMDA receptor modulator
4. ASP-4345 – Positive Allosteric Modulator of D1 Receptors
5. ASP-5736 – 5-HT5A receptor antagonist
6. BMS-955829 – Positive allosteric modulators (PAMs) of the metabotropic glutamate receptor subtype 5 (mGluR5)
7. NBI-1065846 – GPR139 protein agonists
8. samelisant – histamine H3 inverse agonist
9. Plazinemdor – NMDA receptor allosteric agonist
10. VQW-765 – Alpha7 nicotinic acetylcholine receptor agonists
11. VU-0467154 – muscarinic acetylcholine M4 receptor allosteric agonist
12. HTL0048149 – GPR52 agonist
13. SKL-15508 – Alpha7 nicotinic acetylcholine receptor agonists
14. KYN-5356 – Kynurenine-oxoglutarate transaminase inhibitor

For more information about drugs for cognitive and negative symptoms, see this article.
22 Drugs for Cognitive and Negative Symptoms of Schizophrenia

(If a drug is not on the list above, I will add it as soon as I find it.)

References

• https://en.wikipedia.org/wiki/List_of_investigational_antipsychotics
• https://www.gii.co.jp/report/labd1000812-cognitive-impairment-associated-schizophrenia-cias.html