[Discovery of an antiparkinsonian drug: zonisamide].
[Discovery of an antiparkinsonian drug: zonisamide].
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[抗帕金森病药物：唑尼沙胺的发现]。
DOI：
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发表时间：
2010
期刊：
影响因子：
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通讯作者：
M. Murata
中科院分区：
文献类型：
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作者：
M. Murata
我们发现唑尼沙胺 (ZNS) 是一种抗癫痫药，对帕金森病具有有益作用。每天一次 25 毫克的 ZNS 可显着改善晚期帕金森病患者的运动功能。即使对于晚期患者，其效果也能维持至少一年。最终于2009年3月在日本被批准为抗帕金森病药物。ZNS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。它中度抑制单胺氧化酶 (MAO) 活性。 ZNS对T型Ca(++)通道的抑制作用也可能影响其抗帕金森病的作用。 ZNS 还通过影响神经元和神经胶质细胞对几种帕金森病模型显示出神经保护作用。我们将验证ZNS对帕金森病患者的神经保护作用，并通过近期特征的全基因组关联研究（GWAS）研究导致唑尼沙胺效果个体差异的因素。
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.