Compound 7 was excluded from this evaluation due to its similarity to THA. We tested the derivatives by the whole-cell patch-clamp method at a concentration of 10 μM under steady-state conditions at membrane potentials of -60 or +40 mV in the presence of the saturating concentrations of NMDAR (co-agonists L-glutamate and glycine). Our measurements showed that all tested derivatives exhibited inhibition toward the GluN1/GluN2B receptor, ranging from ~61 to ~88% at membrane potential -60 mV and ~20 to ~88% at membrane potential +40 mV (Table ). The compound 5e exhibited a voltagedependent effect similar to that observed for 7-MEOTA. In contrast, compounds 5a, 5i, and 5m displayed voltage-independent inhibitory effects, suggesting their interaction with the ifenprodilbinding site of the GluN1/GluN2B receptor, akin to 7-PhO-THA. Notably, the inhibitory potency of compounds 5i and 5m was comparable to 7-PhO-THA at both -60 mV and +40 mV and memantine at -60 mV. Concentration-response curve analysis of the most potent compound, 5m, revealed an IC₅₀ value of 2.12 ± 0.23 µM with a Hill coefficient of 1.52 ± 0.13 at a membrane potential of -60 mV (n = 5; Figure ), highlighting the promising potency of these new derivatives at NMDARs. Relative inhibition (RI, % ± SEM) of selected compounds at GluN1/GluN2B NMDARs measured at the steady-state conditions at membrane potentials of -60 or +40 mV, where n equals the number of analyzed cells.