NYX-2925 (NYX2925) is a potent, specific NMDAR positive allosteric-modulator, facilitates [3H] MK-801 binding in all four human NMDAR2 subtypes with EC50 of 55 pM, 28 fM, 11 pM, and 55 pM for hNR2A, 2B, 2C, and 2D receptors, respectively.
NYX-2925 does not exhibit any significant affinity for a large panel of neuroactive receptors, including hERG receptors.
NYX-2925 increased MK-801 binding to human N-methyl-D-aspartate receptor NR2A-D subtypes expressed in HEK cells and enhanced N-methyl-D-aspartate receptor current and long-term potentiation (LTP) in rat hippocampal slices (100–500 nM).
NYX-2925 showed increased metaplasticity in a hippocampal LTP paradigm and structural plasticity 24 hours after administration (1 mg/kg p.o.).
NYX-2925, like rapastinel, activates an NMDA receptor-mediated synaptic plasticity process and may have therapeutic potential for a variety of NMDA receptor-mediated central nervous system disorders.