Dooley M, Markham A
Adis International Limited, Auckland, New Zealand.
Drugs Aging. 1998 Jun;12(6):495-514. doi: 10.2165/00002512-199812060-00007.
Pramipexole is an orally active non-ergoline dopamine agonist with selective activity at dopamine receptors belonging to the D2 receptor subfamily (D2, D3, D4 receptor subtypes) and with preferential affinity for the D3 receptor subtype. It is approved as monotherapy in early Parkinson's disease and as adjunctive therapy to levodopa in patients with advanced disease experiencing motor effects because of diminished response to levodopa. The potential neuroprotective effects of pramipexole have been shown in animal and in vitro studies. Data from relatively long term (10- or 31-week) studies suggest that pramipexole monotherapy (0.375 to 6.0 mg/day) can improve activities of daily living and motor symptoms in patients with early Parkinson's disease. Pramipexole (0.375 to 4.5 mg/day for 31 or 36 weeks), as an adjunct to levodopa in advanced disease, improved activities of daily living and motor symptoms, reduced the duration and severity of 'off' periods and allowed a reduction in levodopa dosage. Mentation, behaviour and mood [Unified Parkinson's Disease Rating Scale (UPDRS) part I], and timed walking test were not significantly improved. The extent of disability improved according to the UPDRS parts II and III but, when assessed by secondary efficacy parameters, it is unclear whether disability or the severity of disease improved. No significant differences were observed in patients randomised to pramipexole or bromocriptine according to a secondary hypothesis in a prospective study in which both drugs were better than placebo. Some quality-of-life measures improved with active treatment relative to placebo. Further studies comparing pramipexole with other dopamine agonists and levodopa in patients with early and advanced Parkinson's disease would be useful. In pramipexole recipients with early disease, the most commonly experienced adverse events were nausea, dizziness, somnolence, insomnia, constipation, asthenia and hallucinations. The most commonly reported adverse events in pramipexole recipients with advanced disease were orthostatic hypotension, dyskinesias, extrapyramidal syndrome (defined as a worsening of the Parkinson's disease), dizziness, hallucinations, accidental injury, dream abnormalities, confusion, constipation, asthenia, somnolence, dystonia, gait abnormality, hypertonia, dry mouth, amnesia and urinary frequency. The incidence of some adverse events did not greatly differ between pramipexole and placebo recipients.
Pramipexole is effective as adjunctive therapy to levodopa in patients with advanced Parkinson's disease. However, the potential beneficial effects of pramipexole on disease progression need to be confirmed in clinical studies. The efficacy of pramipexole monotherapy in patients with early disease has also been demonstrated, although the use of dopamine agonists in early Parkinson's disease remains controversial.
普拉克索是一种口服活性非麦角林多巴胺激动剂，对属于D2受体亚家族的多巴胺受体（D2、D3、D4受体亚型）具有选择性活性，对D3受体亚型具有优先亲和力。它被批准用于早期帕金森病的单药治疗，以及用于晚期帕金森病患者因左旋多巴反应减弱而出现运动症状时作为左旋多巴的辅助治疗。普拉克索的潜在神经保护作用已在动物和体外研究中得到证实。相对长期（10周或31周）研究的数据表明，普拉克索单药治疗（0.375至6.0毫克/天）可改善早期帕金森病患者的日常生活活动能力和运动症状。普拉克索（0.375至4.5毫克/天，持续31或36周）作为晚期疾病左旋多巴的辅助药物，改善了日常生活活动能力和运动症状，减少了“关”期的持续时间和严重程度，并允许减少左旋多巴剂量。精神状态、行为和情绪[统一帕金森病评定量表（UPDRS）第一部分]以及定时步行试验没有显著改善。根据UPDRS第二和第三部分，残疾程度有所改善，但通过次要疗效参数评估时，尚不清楚残疾或疾病严重程度是否得到改善。在前瞻性研究中，根据次要假设，随机接受普拉克索或溴隐亭治疗的患者之间未观察到显著差异，在该研究中两种药物均优于安慰剂。与安慰剂相比，积极治疗使一些生活质量指标得到改善。进一步比较普拉克索与其他多巴胺激动剂以及左旋多巴在早期和晚期帕金森病患者中的研究将是有益的。在早期疾病的普拉克索接受者中，最常出现的不良事件是恶心、头晕、嗜睡、失眠、便秘、乏力和幻觉。晚期疾病的普拉克索接受者中最常报告的不良事件是体位性低血压、运动障碍、锥体外系综合征（定义为帕金森病恶化）、头晕、幻觉、意外伤害、梦境异常、意识模糊、便秘、乏力、嗜睡、肌张力障碍、步态异常、张力亢进、口干、失忆和尿频。普拉克索和安慰剂接受者之间一些不良事件的发生率差异不大。
普拉克索作为晚期帕金森病患者左旋多巴的辅助治疗是有效的。然而，普拉克索对疾病进展的潜在有益作用需要在临床研究中得到证实。普拉克索单药治疗对早期疾病患者的疗效也已得到证实，但多巴胺激动剂在早期帕金森病中的应用仍存在争议。
