Neuroprotective effect of riluzole in MPTP-treated mice

The neuroprotective effects of riluzole, a Na+ channel blocker with antiglu tamatergic activity, and MK-801, a blocker of N-methyl-D-aspartate (NMDA) r eceptors, were compared in the model of 1-methyl-4-phenyl-1,2,3,6-tetrahydr opyridine (MPTP)-induced depletion of dopamine, 3,4-dihydroxyphenylacetic a cid (DOPAC) and homovanillic acid (HVA) levels in mice. The mice were injec ted intraperitoneally (i.p.) with four administrations of MPTP (10 mg/kg) a t I h intervals and then the brains were analyzed 1, 3 and 7 days after the treatment. Dopamine and DOPAC levels were significantly decreased in the s triatum from 1 day after MPTP treatment. A severe depletion in dopamine and DOPAC levels was found in the striatum 3 and 7 days after MPTP treatment. Riluzole antagonized the MPTP-induced decrease in dopamine, DOPAC and HVA l evels in the striatum. On the other hand, MK-801 prevented the MPTP-induced decrease in DOPAC levels, but not in dopamine levels in the striatum. An i mmunohistochemical study indicated that riluzole can protect against MPTP-i nduced neuronal damage in the substantia nigra. These results suggest that riluzole is effective against MPTP-induced neurodegeneration of the nigrost riatal dopaminergic neuronal pathway. (C) 2001 Elsevier Science B.V. All ri ghts reserved.