Amantadine regulates the severity of experimental autoimmune encephalomyelitis

Background: Amantadine has been reported to have a neuroprotective effect, and it is therefore expected to have further clinical application. Aim: In this study, we examined the therapeutic effect of the N-methyl-D-aspartate (NMDA) receptor antagonist amantadine on experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). Methods: Experimental autoimmune encephalomyelitis was induced in C57BL/6 mice. Amantadine was administered at doses of 40 mg/kg dissolved in phosphate buffer saline (PBS) by feeding cannula every other day. The control group received PBS only. The immunized mice were examined and scored daily until day 35. T-cell proliferation assay, pathological analysis, and analysis of regulatory cells were performed. Results: Although amantadine did not significantly suppress the incidence or severity of EAE, it significantly reduced clinical symptoms in the recovery phase. There was also a significant increase in CD4(+) CD25(+) Foxp3(+) T cells in response to amantadine treatment. These results suggest that amantadine promotes symptom recovery in EAE by acting in an immunosuppressive manner. Conclusion: Amantadine may be an effective therapy for inflammatory neurological diseases such as MS.