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Neurotropic viruses, such as the rabies virus (RABV) and Japanese encephalitis virus (JEV), induce neuronal dysfunction and complication, causing neuronal damage. Currently, there are still no effective clinical treatments for neuronal injury caused by neurotropic viruses. Memantine, a drug capable of passing through the blood‐brain barrier, noncompetitively and reversibly binds to n‐methyl‐ d‐aspartic acid (NMDA) receptors. Memantine is used to treat Alzheimer's disease by blocking the activation of extra axonal ion channels, thus preventing neuronal degeneration by inhibiting the abnormal cytosolic Ca 2+ increase. To explore whether memantine can alleviate neurological disturbances caused by RABV and JEV, the following experiments were carried out: (1) for primary neurons cultured in vitro infected with RABV, the addition of memantine showed neuroprotection. (2) In the RABV challenge experiments, memantine had limited therapeutic effect, mildly extending the survival time of mice. In contrast, memantine significantly prolonged the survival time of mice infected with JEV, by reducing the intravascular cuff and inflammatory cell infiltration in mice. Furthermore, memantine decreases the amount of JEV virus in mice brain. Highlights: Memantine showed neuroprotection to RABV infected primary neurons.Memantine had mildly extended the survival time of mice infected with RABV.Memantine significantly prolonged the survival time of mice infected with JEV.Memantine decreases the amount of JEV virus in mice brain. [ABSTRACT FROM AUTHOR]