Recent progress in allosteric modulators for GluN2A subunit and development of GluN2A-selective nuclear imaging probes.

N-methyl-D-aspartate (NMDA) receptors play key roles in physiology by regulating the synaptic plasticity and the cellular mechanism involved in learning and memory. The GluN2A subunit is the most abundant expression of NMDA receptors in mature brain, and its dysfunction has been implicated in various neurological disorders. However, the function of GluN2A subunit in physiological and pathological conditions is not yet completely unveil due to the lack of subunit-selective ligands, including specific positron emission tomography (PET)/single photon emission computed tomography (SPECT) imaging probes. In this review, recent progresses in understanding its pathophysiological role, the structure-activity relationship, and the postulated mechanisms of novel GluN2A ligands as well as status of molecular imaging probes for PET are summarized.