Riluzole protects against MPTP induced dopamine and DOPAC depletion in mice

We investigated the neuroprotective effects of riluzole, a Na⁺ channel blocker with antiglutamatergic activity, MK-801, a blocker of N-methyl-D-aspartate (NMDA) receptors, monoamine oxidase (MAO) inhibitor parygline and MAO type-A (MAO-A) selective inhibitor clorgyline in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. The mice received four intraperitoneal injections of MPTP (10 mg/kg) at 1h intervals and then the brains were analyzed at 1,3 and 7 days after MPTP treatments. Dopamine and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) levels were significantly decreased in the striatum from 1 day after MPTP treatments. Thereafter, a severe depletion in dopamine and DOPAC levels was found in the striatum 3 and 7 days after MPTP treatments. Therefore, the evaluation of each compound was performed 3 days after MPTP treatments. Riluzole dose dependently antagonized the MPTP-induced decrease in dopamine and DOPAC levels in the striatum of mice. Pargyline and clorgyline also protected against MPTP-induced decrease in dopamine levels in the striatum of mice. However, these drugs showed no significantly change in the striatal DOPAC levels in MPTP-induced decrease in dopamine levels in the striatum of mice. However, MK-801 reversed the MPTP-induced decrease in DOPAC levels. These results suggest that riluzole can protect against MPTP-induced striatal dopamine and DOPAC depletion in mice. This protective effect may be caused by inactivation of voltage-dependent Na⁺ channels by riluzole. Furthermore, the present study suggests that NMDA receptors are not mainly involved in mediating MPTP-induced neurodegeneration, whereas MAO, especially MAO type-B (MAO-B) plays a crucial role in MPTP-induced degeneration of the nigrostriatal dopaminergic neuronal pathway. These findings demonstrate that riluzole as well as MAO inhibitor may be useful in the treatment of Parkinson's diseases.