GluN2B-NMDAR antagonist-2 (compound S-58) is an effective and selective NMDAR-GluN2B antagonist that can cross the blood-brain barrier, with an IC50 value of 74.01 nM. It exhibits mild cytotoxicity and reduces both infarct size and neurological deficit scores in the brain, indicating its potential for stroke research.

GluN2B:74.01 nM

GluN2B-NMDAR antagonist-2 (compound S-58) (1, 3, 10 µM) does not significantly extend the action potential duration (APD90) in hiPSC-CM. When administered at concentrations ranging from 0 to 300 µM over 48 hours, it exhibits slight cytotoxicity to primary mouse neurons, VERO, L929, and HEK293 cells.

The compound GluN2B-NMDAR antagonist-2, when administered intravenously at doses of 5, 10, and 20 mg/kg, reduces cerebral infarction rates and neurological deficit scores in a dose-dependent manner in the MCAO rat model. In ICR mice, GluN2B-NMDAR antagonist-2 (450, 900 mg/kg; i.v.) demonstrates favorable safety, with a maximum tolerated dose (MTD) of 450 mg/kg.