Abstract: Objective To study the effect of mAbN1, a monoclonal antibody against N-methyl-D-aspartate receptor subunit 1 (NR1) on Ca2+ influx after glutamate stimulation in rat cultured hippocampal neurons. Methods Excitotoxicity was induced by glutamate in cultured hippocampal neurons. Confocal laser scanning microscopy was used to observe the changes in intracellular free calcium concentration ([Ca2+]i) at the level of cultured hippocampal neurons following pretreatment with mAbN1 and MK-801. Intracellular free calcium was imaged after loading cells with the fluorescent dye indicator fluo-3/AM. Results Our findings indicate that compared with MK-801, mAbN1 can more significantly attenuate the glutamate-induced [Ca2+]i increase, and it has no effect on [Ca2+]i in physiological condition. Conclusion mAbN1 maybe alter the secondary structure of NR, consequently influence Ca2+ influx in excitotoxicity process