NMDAR blocker 1

NMDAR blocker 1 is an NMDA receptor channel blocker with an IC50 of 5.0 μM. It features rapid switching block kinetics and strong voltage dependency, without competing for glutamate or glycine binding sites. This compound can prevent intracellular Ca2+ overload induced by glutamate/NMDA and modulates the glutamate-nitric oxide-cGMP pathway. In vitro, NMDAR blocker 1 inhibits excitotoxic neurodegeneration in cultured cerebellar and hippocampal neurons. Additionally, it reduces excitotoxic damage in a mouse model of hyperammonemia-induced excitotoxicity, making it applicable for research into neurodegenerative diseases.

NMDAR blocker 1 effectively and selectively inhibits rat NR1/NR2A NMDA receptor channel activity in Xenopus laevis oocytes, with an IC 50 of 5.0 ± 0.2 μM when used in concentrations of 5-500 μM. It provides neuroprotection to primary cultured rat cerebellar and hippocampal neurons from excitotoxic death within a concentration range of 0.1-100 μM over 4 hours, achieving a maximum cerebellar neuron survival rate of 85 ± 6% at 30 μM. Additionally, NMDAR blocker 1 at concentrations of 0.01-30 μM over 5 minutes dose-dependently inhibits NMDA-induced cGMP production in primary rat cerebellar neurons. Moreover, it potently blocks NMDA-induced intracellular Ca 2+ overload in primary rat cerebellar neurons when administered at concentrations of 0.01-100 μM for 10 minutes, achieving complete inhibition at 100 μM.

NMDAR blocker 1 (Compound N20C) (5-50 μg/g; intraperitoneal injection; single dose) provides dose-dependent neuroprotection in vivo against excitotoxicity induced by acute ammonia in male Swiss mice.