Guttman M
Human Neurochemical Pathology Laboratory, Clarke Institute of Psychiatry, University of Toronto, Canada.
Neurology. 1997 Oct;49(4):1060-5. doi: 10.1212/wnl.49.4.1060.
Pramipexole is a new, selective, nonergoline dopamine agonist that acts on D2 and preferentially on D3 dopamine receptors. Phase II and III clinical trials have shown this drug to be useful in treating both early and advanced Parkinson's disease (PD) patients. A double-blind, randomized, multicenter study was performed to compare the safety, tolerance, and efficacy of pramipexole versus placebo in patients with advanced PD with motor fluctuations. A bromocriptine treatment group was included to enable comparisons between bromocriptine and placebo groups, but the study was not powered to show statistical differences between the active treatment groups. The study included 247 patients with "wearing off." Patients were Hoehn and Yahr stages II to IV during "on" times. The trial included three phases: dose escalation, 6 months' maintenance, and dose reduction. The primary end points were the Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III. Up to 4.5 mg per day of pramipexole and 30 mg per day of bromocriptine were used. The results of the study showed that the UPDRS part II improved by 26.7% for pramipexole (p = 0.0002) and 14% for bromocriptine (p = 0.02) versus 4.8% for placebo. The UPDRS part III showed improvements of 34% for pramipexole (p = 0.0006) and 23.8% for bromocriptine (p = 0.01) versus 5.7% for placebo. There were no major differences in safety data. In the active treatment groups there were more reports of dyskinesia and nausea compared with placebo. In regard to comparison of the Global Clinical Assessment of Efficacy between active treatment groups, there was a trend to significance (p = 0.056) in favor of pramipexole. We conclude that pramipexole-treated patients with advanced PD improved significantly more than placebo for both primary end points.
普拉克索是一种新型、选择性、非麦角林类多巴胺激动剂，作用于D2受体，对D3多巴胺受体具有优先亲和力。II期和III期临床试验表明，该药物对早期和晚期帕金森病（PD）患者均有效。进行了一项双盲、随机、多中心研究，比较普拉克索与安慰剂在晚期PD伴运动波动患者中的安全性、耐受性和疗效。纳入了溴隐亭治疗组，以便在溴隐亭组和安慰剂组之间进行比较，但该研究的样本量不足以显示活性治疗组之间的统计学差异。该研究纳入了247例出现“疗效减退”的患者。患者在“开”期处于Hoehn和Yahr II至IV期。试验包括三个阶段：剂量递增、6个月维持期和剂量递减。主要终点为统一帕金森病评定量表（UPDRS）的第二部分和第三部分。普拉克索每日最高用量为4.5 mg，溴隐亭每日最高用量为30 mg。研究结果显示，与安慰剂组改善4.8%相比，普拉克索组UPDRS第二部分改善了26.7%（p = 0.0002），溴隐亭组改善了14%（p = 0.02）。普拉克索组UPDRS第三部分改善了34%（p = 0.0006），溴隐亭组改善了23.8%（p = 0.01），而安慰剂组改善了5.7%。安全性数据方面无重大差异。与安慰剂组相比，活性治疗组出现异动症和恶心的报告更多。关于活性治疗组之间的整体临床疗效评估比较，有倾向于普拉克索的显著趋势（p = 0.056）。我们得出结论，对于两个主要终点，普拉克索治疗的晚期PD患者比安慰剂组有更显著的改善。
