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.

However, unlike rapastinel, zelquistinel is orally bioavailable, exhibits increased potency, and has improved drug properties.

[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] 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.