Murata Miho
Department of Neurology, National Center Hospital, National Center of Neurology & Psychiatry.
Rinsho Shinkeigaku. 2010 Nov;50(11):780-2. doi: 10.5692/clinicalneurol.50.780.
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.
我们发现抗癫痫药物唑尼沙胺（ZNS）对帕金森病有有益作用。每天一次服用25毫克的唑尼沙胺能显著改善晚期帕金森病患者的运动功能。即使在晚期患者中，其效果也能维持至少一年。最终，它于2009年3月在日本被批准为抗帕金森病药物。唑尼沙胺通过增加酪氨酸羟化酶（TH）mRNA和TH蛋白的水平来激活多巴胺合成，从而增加纹状体中的多巴胺含量。它适度抑制单胺氧化酶（MAO）的活性。唑尼沙胺对T型钙通道的抑制作用也可能影响其抗帕金森病的效果。唑尼沙胺还通过影响神经元和神经胶质细胞，对多种帕金森病模型显示出神经保护作用。我们将在近期通过全基因组关联研究（GWAS）验证唑尼沙胺对帕金森病患者的神经保护作用，并研究导致唑尼沙胺疗效个体差异的因素。
