TY - JOUR A2 - Stocchi，法布里奇奥AU - 西岛，春夫AU - 三木康夫AU - 上野真矢AU - 富山，正彦PY - 2018 DA - 二〇一八年十二月十八日TI - 左旋多巴的唑尼沙胺提高了电机的影响，而不是阿朴吗啡, in a Rat Model of Parkinson’s Disease SP - 8626783 VL - 2018 AB - Zonisamide is a relatively recent drug for Parkinson’s disease. Multiple hypotheses have been proposed to explain the antiparkinsonian effects of zonisamide. However, it is still unclear whether the effect of zonisamide is mainly due to dopaminergic modification in the striatum, or if zonisamide works through nondopaminergic pathways. We conducted the present study to determine the mechanism that is mainly responsible for zonisamide’s effects in Parkinson’s disease. We examined the effects of zonisamide on motor symptoms in a hemiparkinsonian rat model when administered singly, coadministered with levodopa, a dopamine precursor, or apomorphine, a D1 and D2 dopamine receptor agonist. We used 6-hydroxydopamine-lesioned hemiparkinsonian rats, which were allocated to one of five groups: 14 rats received levodopa only (6 mg/kg), 12 rats received levodopa (6 mg/kg) plus zonisamide (50 mg/kg), six rats received apomorphine only (0.05 mg/kg), six rats received apomorphine (0.05 mg/kg) plus zonisamide (50 mg/kg), and six rats received zonisamide only (50 mg/kg). The drugs were administered once daily for 15 days. We evaluated abnormal involuntary movement every 20 min during a 3 h period following the injection of drugs on treatment Days 1, 8, and 15. Western blot analyses for dopamine decarboxylase and vesicular monoamine transferase-2 were performed using striatal tissues in the lesioned side of rats in the levodopa only group ( ñ= 6）和左旋多巴加唑尼沙胺组（ ñ= 4）。左旋多巴引起的异常不自主运动用的唑尼沙胺共施用显著增强。相比之下，唑尼沙胺对阿朴吗啡诱发异常不自主运动没有影响。唑尼沙胺单药治疗没有引起异常的不自主运动。唑尼沙胺不影响多巴胺脱羧酶或囊泡单胺转移酶2的纹状体表达。总之，唑尼沙胺似乎产生由帕金森纹状体调节左旋多巴多巴胺代谢的抗帕金森病的效果。SN - 2090-8083 UR - https://doi.org/10.1155/2018/8626783 DO - 10.1155 /八百六十二万六千七百八十三分之二千○一十八JF - 帕金森病PB - Hindawi出版KW - ER -