Abstract: Objective To explore the protective effect and mechanism of oxiracetam on primary fetal rat cortical neurons and to analyze the key sites of oxiracetam acting on N-methyl-D-aspartic acid receptor (NMDA). 
Methods By using calcium ion imaging technology and molecular docking techniques on primary fetal rat cortical neurons, the protective effect of oxacetam on neurons were described at the cellular and molecular level and the molecular mechanism was analyzed. 
Results The results of cell culture of primary fetal rat cortical neurons showed that oxiracetam could ameliorate glutamate-induced neurotoxicity.Incubation with oxiracetam at varying concentration gradients for 1 min down-regulated glutamate-induced intracellular calcium ion (［Ca2+］i) elevation in a dose-response effect. As the concentration of oxiracetam increased to 30 μmol/L, the peak calcium concentration caused by glutamate was significantly reduced to (78.45±3.12)%, and the area under the curve (AUC) decreased to (77.06±1.39)%. Increasing the concentration of oxiracetam further did not result in significant changes in the peak calcium concentration.The final calculation showed that half maximal inhibitory concentration (IC50)of oxiracetam on peak increase in glutamate-induced ［Ca2+］i concentration was 15.34 μmol/L and that of AUC was 14.26 μmol/L, respectively. Oxiracetam binded to NMDA receptors at ASN-599, LEU-601, PRO-602, and GLN-604, with a binding energy of -3.34 kcal/mol. 
Conclusion Oxiracetam can effectively bind to glutamate receptors and play a neuroprotective role in improving glutamate-induced intracellular calcium overload.

Key words: oxiracetam, neurons, calciumion