The low-affinity use-dependent N-methyl-D-aspartate (NMDA) receptor antagon
ist AR-R15896AR is neuroprotective in primary rat cortical cultures exposed
to toxic concentrations of NMDA and reduces the magnitude of: NMDA-trigger
ed increases in [Ca2+](i). Here we show using fluorescence staining and mea
surements of microtubule-associated protein-2 (MAP2) levels, that AR-R15896
AR inhibits the NMDA-induced loss of MAP2 that occurs within 2 min followin
g NMDA exposure. Understanding the multiple, Ca2+-triggered intracellular e
vents that occur following NMDA receptor stimulation is important to the de
velopment of safe and effective neuroprotective agents.