 | |
 Above: Zelquistinel structure
Below: 3D representation of a zelquistinel molecule | |
| Clinical data | |
|---|---|
| Routes of administration | By mouth |
| Drug class | NMDA receptor positive allosteric modulator |
| Pharmacokinetic data | |
| Bioavailability | ~100% |
| Elimination half-life | 1.2–2 hours |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| ChemSpider | |
| UNII | |
| Chemical and physical data | |
| Formula | C15H25N3O5 |
| Molar mass | 327.381 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
Zelquistinel (GATE-251, formerly AGN-241751) is an orally active small-molecule NMDA receptor positive allosteric modulator which is under development for the treatment of major depressive disorder (MDD) by Syndeio Biosciences, and previously by Allergan.123
Pharmacology
Zelquistinel acts through a unique binding site on the NMDA receptor, independent of the glycine site, to positively modulate receptor activity and enhance NMDAR-mediated synaptic plasticity.45 Its mechanism of action is similar to that of rapastinel. However, unlike rapastinel, zelquistinel is orally bioavailable, exhibits increased potency, and has improved drug properties.235 The mean half-life of Zelquistinel is reported to be from 1.21 to 2.06 hours, reaching peak plasma concentrations 30 minutes after administration.6
In preclinical studies, single doses of zelquistinel demonstrated both rapid-acting (24-hours) and sustained (1-week) antidepressant-like effects and enhancement of long-term synaptic plasticity.6
Clinical development
On July 23, 2018, the U.S. FDA granted Fast Track designation to the development of zelquistinel as an investigational new treatment for major depressive disorder.7
In 2019, Allergan completed an exploratory phase IIa clinical trial of once-weekly oral zelquistinel in major depressive disorder.138 By week three, the two highest doses studied reduced MADRS depression scores by 9.5 and 10.6 points compared to a 7.7-point reduction with placebo. This result was considered statistically and clinically significant.8
As of 2025, zelquistinel is undergoing a phase IIb clinical trial for depression sponsored by Syndeio Biosciences.2
See also
See also
References
References
- "NMDA receptor modulators - AdisInsight". adisinsight.springer.com.
- "Home - Gate Neurosciences". Retrieved 2022-05-12.
- Aptinyx Inc. "Allergan Exercises Option to Acquire Compound from Aptinyx Discovery Platform Under Ongoing Research Collaboration". www.prnewswire.com (Press release).
- Donello JE, Banerjee P, Li YX, Guo YX, Yoshitake T, Zhang XL, et al. (March 2019). "Positive N-Methyl-D-Aspartate Receptor Modulation by Rapastinel Promotes Rapid and Sustained Antidepressant-Like Effects". The International Journal of Neuropsychopharmacology. 22 (3): 247–259. doi:10.1093/ijnp/pyy101. PMC 6403082. PMID 30544218.
- Pothula S, Liu RJ, Wu M, Sliby AN, Picciotto MR, Banerjee P, Duman RS (March 2021). "Positive modulation of NMDA receptors by AGN-241751 exerts rapid antidepressant-like effects via excitatory neurons". Neuropsychopharmacology. 46 (4): 799–808. doi:10.1038/s41386-020-00882-7. PMC 8027594. PMID 33059355.
- Burgdorf JS (26 July 2022). "Zelquistinel Is an Orally Bioavailable Novel NMDA Receptor Allosteric Modulator That Exhibits Rapid and Sustained Antidepressant-Like Effects". International Journal of Neuropsychopharmacology.
- plc A. "Allergan Receives FDA Fast Track Designation for AGN-241751 for the Treatment of Major Depressive Disorder (MDD)". www.prnewswire.com (Press release). Retrieved 2022-05-16.
- Clinical trial number NCT03586427 for "A Double-Blind, Placebo-Controlled, Fixed-Dose Study of AGN-241751 in Adult Participants With Major Depressive Disorder" at ClinicalTrials.gov