Zelquistinel Explained
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 Gate Neurosciences, and previously by Allergan.[1] [2] [3]
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. 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.
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. As of 2024, zelquistinel is undergoing a phase IIb clinical trial for depression sponsored by Gate Neurosciences.
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Notes and References
- Web site: NMDA receptor modulators - AdisInsight . adisinsight.springer.com.
- Web site: Home - Gate Neurosciences . 2022-05-12 . en-US.
- Aptinyx Inc. . Allergan Exercises Option to Acquire Compound from Aptinyx Discovery Platform Under Ongoing Research Collaboration . www.prnewswire.com.
- 6 . Donello JE, Banerjee P, Li YX, Guo YX, Yoshitake T, Zhang XL, Miry O, Kehr J, Stanton PK, Gross AL, Burgdorf JS, Kroes RA, Moskal JR . 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 . 10.1093/ijnp/pyy101 . 6403082 . 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 . 10.1038/s41386-020-00882-7 . 8027594 . 33059355.
- Burgdorf . Jeffrey S. . 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 . Allergan . Allergan Receives FDA Fast Track Designation for AGN-241751 for the Treatment of Major Depressive Disorder (MDD) . 2022-05-16 . www.prnewswire.com . en.
