NMDA receptor antagonist 4 (IIc) is a uncompetitive, voltage-dependent, orally active NMDAR blocker, with an IC50 of 1.93 ?M. NMDA receptor antagonist 4 shows a positive predicted blood-brain-barrier (BBB) permeability, and can be studied in Alzheimer's disease[1].
NMDA receptor antagonist 4 (IIc) shows competitive interaction with endogenous blocker Mg2+, and shows dependence on membrane potential in the NMDAR channel[1].NMDA receptor antagonist 4 shows high metabolic stability in human and mice liver microsomes, and shows hERG safety, without obvious cytotoxicity[1].
NMDA receptor antagonist 4 (IIc) (0-10 ?M) rescues the motor deficits, and protects against Aβ toxicity-related neuronal dysfunction[1].NMDA receptor antagonist 4 (5 mg/kg/day; p.o.; 4 weeks) improves cell survival and synaptic function in AD through increasing the activity of cell-survival signaling pathways (Fyn-GluN2B-CREB signaling) and preventing internalization of synaptic NMDARs[1].
References:
[1]. Andreea L. Turcu, et al. Design, synthesis, and in vitro and in vivo characterization of new memantine analogs for Alzheimer's disease. Eur J Med Chem. 2022 Apr 8;236:114354.