Chemistry:Matsupexole
Matsupexole (INN; developmental code names AM006 and KDT-3594) is a dopamine receptor agonist which is under development for the treatment of Parkinson's disease.[1][2][3][4][5] It is taken orally.[1][3]
The drug is a non-ergoline derivative related to pramipexole and acts as a dopamine D2 and D3 receptor agonist.[5][4][6] It has far lower selectivity for the dopamine D3 receptor over the dopamine D2 receptor than pramipexole and other non-ergoline dopamine receptor agonists.[5] Relatedly, whereas pramipexole and other non-ergoline dopamine receptor agonists like ropinirole and rotigotine produce somnolence in humans and pramipexole has been found to strongly promote non-REM sleep in rodents, these side effects being associated with dopamine D3 receptor agonism, matsupexole and cabergoline did not promote non-REM sleep at efficacious antiparkinsonian doses in rodents.[5] This may be due to a better balance of wakefulness-promoting dopamine D2 receptor activation versus sedating dopamine D3 receptor activation.[5] Similarly to pramipexole, but unlike cabergoline, matsupexole showed negligible activity as a serotonin 5-HT2B receptor agonist and hence is not thought to have a risk of cardiac valvulopathy.[5]
Matsupexole was first described in the scientific literature by 2017.[7] It originated by Kissei Pharmaceutical and is being developed by Kissei Pharmaceutical and AffaMed Therapeutics in Japan and China.[1][2][3] As of August 2025, the drug is in phase 2 clinical trials.[1][2][3] Matsupexole is described by its developers as a potential best-in-class dopamine receptor agonist for Parkinson's disease.[5]
See also
- List of investigational Parkinson's disease drugs
References
- ↑ 1.0 1.1 1.2 1.3 "Kissei Pharmceutical". 28 August 2025. https://adisinsight.springer.com/drugs/800045528.
- ↑ 2.0 2.1 2.2 "Delving into the Latest Updates on Matsupexole with Synapse". 24 January 2026. https://synapse.patsnap.com/drug/19a7e26a630e4a53b76c7fe546285d59.
- ↑ 3.0 3.1 3.2 3.3 "Matsupexole Drug Profile". 1 January 1900. https://pryzm.ozmosi.com/product/24588.
- ↑ 4.0 4.1 "Recent advances in dopaminergic strategies for the treatment of Parkinson's disease". Acta Pharmacologica Sinica 41 (4): 471–482. April 2020. doi:10.1038/s41401-020-0365-y. PMID 32112042. "KDT3594 (structure undisclosed) is a D2 agonist developed by Kissei Pharmaceuticals [16]. A phase 2 study was initiated in February 2019 to investigate the efficacy, safety, and PK of KDT3594 vs. pramipexole in patients with early PD without concomitant treatment with L-DOPA (NCT03845387).".
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 "Matsupexole: A novel nonergot dopamine receptor agonist with sustained efficacy in a rat model of Parkinson's disease and limited off-target activity". British Journal of Pharmacology. January 2026. doi:10.1111/bph.70351. PMID 41578631.
- ↑ "Motor fluctuations in Parkinson disease - a mini-review of emerging drugs". Expert Opinion on Emerging Drugs: 1–12. June 2025. doi:10.1080/14728214.2025.2517582. PMID 40500235. "Two other dopamine agonists have been evaluated in PD with motor fluctuations, but results are pending. KDT-3594 (matsupexole) is another non-ergot DA targeting dopamine D2 receptors [40] also currently in a phase II trial in individuals with advanced PD (ClinicalTrials.gov Identifier: NCT06722729).".
- ↑ "Current approaches to the treatment of Parkinson's Disease". Bioorganic & Medicinal Chemistry Letters 27 (18): 4247–4255. September 2017. doi:10.1016/j.bmcl.2017.07.075. PMID 28869077. "Kissei Pharmaceuticals features a D2 agonist, KDT3594, on their pipeline chart in Phase 1 for PD.33 The structure has not been published, and there are no current US clinical trials listed.".
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