Zelquistinel
Investigational antidepressant compound
From Wikipedia, the free encyclopedia
Zelquistinel (GATE-251, formerly AGN-241751) is an orally active small-molecule NMDA receptor modulator which is under development for the treatment of major depressive disorder (MDD) by Syndeio Biosciences, and previously by Allergan.[1][2][3]
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 Above: Zelquistinel structure
Below: 3D representation of a zelquistinel molecule | |
| Clinical data | |
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| Routes of administration | By mouth |
| Drug class | NMDA receptor modulator |
| Pharmacokinetic data | |
| Bioavailability | ~100% |
| Elimination half-life | 1.2–2 hours |
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| Chemical and physical data | |
| Formula | C15H25N3O5 |
| Molar mass | 327.381 g·mol−1 |
| 3D model (JSmol) | |
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Pharmacology
Zelquistinel acts through a unique binding site on the NMDA receptor, independent of the glycine site, to modulate receptor activity and enhance NMDAR-mediated synaptic plasticity.[4][5] 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.[2][3][5] 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.[1][3][8] 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]
