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[摘要]：Zonisamide, a benzisoxazole derivative, is an antiepileptic drug with a long half-life. Three nationwide, double-blind, placebo-controlled studies carried out in Japan prompted the approval of zonisamide as an antiparkinsonian agent in early 2009. The addition of zonisamide at 25-50 mg/day to currently used antiparkinsonian drugs significantly improved cardinal symptoms in patients with advanced Parkinson's disease. The effects were maintained over more than 1 year even in patients with advanced disease. Zonisamide has multiple modes of action, and its effects on Parkinson's disease include activation of dopamine synthesis, inhibition of monoamine oxidase, inhibition of T-type calcium channels and inhibition of an indirect pathway in the basal ganglia through the delta opioid receptor Furthermore, zonisamide exhibits neuroprotective effects in animal models of Parkinson's disease. It strongly inhibits quinoprotein formation and markedly increases glutathione S-transferase levels in the striatum by enhancing the astroglial cysteine transport system and/or astroglial proliferation via S100 beta production and secretion. |
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