JNJ-GluN2D NAM

JNJ-GluN2D NAM is a novel, selective negative allosteric modulator (NAM) of GluN2D-containing N-methyl-D-aspartate receptors (NMDARs) developed by Johnson & Johnson [1]. The GluN2D subunit is selectively expressed in GABAergic interneurons, and its inhibition reduces inhibitory tone on primary pyramidal cells, leading to a downstream surge in neurotransmitter release (including dopamine, serotonin, and acetylcholine) and enhanced synaptic plasticity [1]. Preclinical studies in rodents demonstrate that JNJ-GluN2D NAM increases synaptogenesis and enhances EEG gamma band power, recapitulating the rapid antidepressant-like effects of non-selective NMDAR antagonists (such as ketamine) without disrupting pre-pulse inhibition, suggesting a lack of dissociative side effects [1]. It is being investigated as a potential therapeutic mechanism for the treatment of depression.