A new perspective on betaine: Targeting the glycine binding site of the NMDA receptor.

Betaine, a methylated glycine derivative, shows promise in treating neuropsychiatric and neurological disorders, but its mechanisms remain unclear. This study investigates betaine's concentration-dependent effects on NMDA receptor-mediated excitatory field potentials (EFPs) in mouse medial prefrontal cortex slices and calcium influx in cultured cortical neurons. We further assessed subtype specificity using HEK293 cells stably expressing GluN1/GluN2A, GluN1/GluN2B, or GluN1/GluN2C NMDA receptor subtypes, measuring calcium flux and single-channel activity.