JNJ-78911118 is a potent, centrally-penetrant, selective antagonist of GluN2A-containing NMDA receptors, blocks GluN1/2AR-induced calcium flux with IC50 of 46 nM.
JNJ-78911118 acts selectively as a negative allosteric modulator of both di- and triheteromeric GluN2A receptors.
JNJ-78911118 shows no activity against GluN1/2B and GluN1/2C receptors and no meaningful activity or GluN1/2D receptors.
JNJ-78911118 binds to the GluN1/2A interface and is a NAM of glycine activity.
JNJ-78911118 produces dose-dependent exposures in plasma and brain, as well as dose-dependent hippocampal receptor occupancy in rats.
JNJ-78911118 produced concentration-dependent receptor occupancy, increased prefrontal cortex monoamine levels in wild type, but not in GluN2A knockout mice, and blocked theta burst induced LTP in the hippocampus.
JNJ-78911118 produced increases in dendritic complexity and synapse number in vitro, and increased mEPSC frequency in rat cortical neurons in vivo.