The monoclonal antibody MABN1 against NMDAR could protect the neurons from excitotoxicity, but the mechanism is unknown. Cultured hippocampus neurons treated with glutamate or/and NMDAR antagonist (MABN1 and MK-801) were studied by FTIR spectroscopy. Spectroscopic differences were observed between MABN1-treated and MK-801-treated samples. Curve-fitting of the deconvoluted amideⅠband revealed the difference of protein second structure between MABN1-protected neurons and glutamate-treated neurons, by which it was presumed that MABN1 protects neurons against excitotoxicity by the mechanism different from the one of MK-801.