Subunit-selective inhibition of N-methyl-d-aspartate receptors (NMDARs) is a promising therapeutic strategyfor several neurological disorders, including epilepsy, Alzheimer’sand Parkinson’s disease, depression, and acute brain injury.We previously described the dihydroquinoline–pyrazoline (DQP)analogue 2a (DQP-26) as a potent NMDAR negativeallosteric modulator with selectivity for GluN2C/D over GluN2A/B.However, moderate (<100-fold) subunit selectivity, inadequate cell-membranepermeability, and poor brain penetration complicated the use of 2a as an in vivo probe. Here, GRIN2C is linked to depressive disorder.