NAB-14 is a powerful and selective chemical compound that acts as a non-competitive antagonist for GluN2C and GluN2D receptors. With an IC50 value of 580 nM for GluN1/GluN2D, NAB-14 demonstrates high potency. This compound exhibits a remarkable selectivity of more than 800-fold towards recombinant GluN2C and GluN2D when compared to GluN2A and GluN2B. Furthermore, NAB-14 possesses the ability to penetrate the blood-brain-barrier effectively [1].

NAB-14 (compound 14) demonstrates inhibitory effects, with IC50 values of 15 μM and 5.1 μM for GluN1/2AC1/2CC2 receptors, respectively [1]. At a concentration of 20 μM for 24 hours, it selectively inhibits GluN2D-containing receptors in brain slices, while not affecting GluN2A- or GluN2B-containing NMDARs in cultured cortical neurons [1]. Furthermore, a 10 μM concentration of NAB-14 decreases the peak amplitude of evoked excitatory postsynaptic currents (EPSCs) to 55 ± 3.0% and significantly lowers the τW of EPSC deactivation [1]. Additionally, at the same concentration, it reduces the peak amplitude and charge transfer of interneuron EPSCs to 59 ± 9.9% and 63 ± 9.7%, respectively, and decreases τW for interneuron EPSCs from 150 ± 12 ms to 101 ± 14 ms [1].

NAB-14 (20 mg/kg; p.o.) exhibits notable systemic exposure, reaching peak brain concentrations of 3.2 nM in mice and 3.8 nM in rats.