Pharmacological characterisation of JNJ-78911118, a novel, centrally-penetrant, selective GluN2A antagonist.
British journal of pharmacology May 13, 2025 Brian Lord, Sirak Simavorian, Ian Fraser et al. 2 citations
A selective GluN2A antagonist, JNJ-78911118, blocks GluN1/2A receptors with an IC50 of 44 nM and shows selectivity over other NMDA receptor subtypes. It increases prefrontal cortex monoamine levels in wild-type but not GluN2A knockout mice, blocks hippocampal long-term potentiation, and boosts dendritic complexity, synapse number, and mEPSC frequency in rat cortical neurons. In rats, no Olney's lesions occurred, but acute increases in heart rate and blood pressure were detected. The molecule reproduces effects of known rapidly acting antidepressants on neurotransmitter levels and synaptic plasticity, offering a tool to study GluN2A biology.