Rapastinel (acetate)

Rapastinel acetate (GLYX-13 acetate) is an N-methyl-D-aspartate (NMDA) receptor modulator with long-acting antidepressant activity. Rapastinel acetate exerts its antidepressant effects by enhancing long-term potentiation (LTP) of synaptic transmission. Rapastinel acetate transiently enhances NMDAR-mediated currents in pyramidal neurons in the hippocampus and medial prefrontal cortex by binding to unique sites on the NMDAR complex. Rapastinel acetate significantly enhanced NMDAR-mediated currents at a concentration of 1 μmol/l and significantly reduced the currents at a concentration of 10 μmol/l. The mechanism of action of Rapastinel acetate is related to the reduction of affinity to intracellular calcium inactivation sites, which provides a theoretical basis for enhancing conductance mediated by NMDAR[1].

[1]Burgdorf J, et al. The long-lasting antidepressant effects of rapastinel (GLYX-13) are associated with a metaplasticity process in the medial prefrontal cortex and hippocampus. Neuroscience. 2015 Nov 12;308:202-11.|[2]Extracellular application of the N-methyl-D-aspartate receptor allosteric modulator rapastinel acts remotely to regulate Ca2+ inactivation at an intracellular locus