Abstract: H₂S has a role of protecting neurons from ischemia-reperfusion injury and significantly reducing the cerebral infarction area, but high concentration of H₂S can induce neurotoxicity. Memantine, a N-methyl-D-aspartic acid(NMDA)receptor antagonist, could reduce the neurotoxicity of H₂S at high concentration. Nine novel structures(compounds I ₁- I ₉)were designed by coupling(4-hydroxy phenyl)-3H-1, 2-dithiole-3-thione(ADT-OH)with memantine through alkanes as linkers and synthesized by four-step reactions from ADT-OH. Their neuroprotection against damage induced by glutamate on HT-22 cells was evaluated by MTT method. The results indicated that these compounds markedly increased the survival rates of damaged HT-22 cells at the concentration of 1 μmol/L(P< 0. 01), which suggested that these compounds could preferably protect neurons against damage induced by glutamate.