[Discovery of an antiparkinsonian drug: zonisamide]

We found that zonisamide (ZNS), an antiepileptic agent, has beneficial effects on Parkinson disease. A 25mg once a day of ZNS significantly improves motor function of advanced patients with Parkinson disease. Its effects maintained at least one year even in patients with advanced stage. It was finally approved as an anti parkinsonian agent in Japan on March 2009. ZNS increases dopamine contents in the striatum by activating dopamine synthesis through increasing the levels of tyrosine hydroxylase (TH) mRNA and TH protein. It moderately inhibits monoamine oxydase (MAO) activity. The inhibitory effect of ZNS on T-type Ca(++)channel may also affect the anti-parkinsonian effects. ZNS also showed neuroprotective effects on several parkinsonian models through effecting both neuron and glia. We will verify the neuroprotective effects of ZNS on patients with Parkinson disease and study the factors responsible for the individual difference of the effects of zonisamide by using genome wide association study (GWAS) in the near feature.