Lambert D, Waters C H
University of Southern California, Department of Neurology, Los Angeles, USA.
Drugs Aging. 2000 Jan;16(1):55-65. doi: 10.2165/00002512-200016010-00005.
In recent years, the treatment of Parkinson's disease has undergone an immense amount of research, resulting in the development of multiple new medications. This has largely been fuelled by dissatisfaction over the development of motor complications secondary to long term levodopa therapy. Different treatment approaches are applied depending on the stage of Parkinson's disease. In early and mild Parkinson's disease, selegiline offers a limited symptomatic effect. Its neuroprotective effect, although at present theoretical, has questionable clinical relevance. Increased mortality associated with selegiline has been reported, although a meta-analysis of 5 different trials did not support this finding. The newer, non-ergoline dopamine agonists, pramipexole and ropinirole, have undergone extensive studies to evaluate their efficacy as monotherapy in early Parkinson's disease. These newer agonists are ideal initial symptomatic medications, primarily because they delay the onset of levodopa-induced motor fluctuations. Efficacy of the newer dopamine agonists in advanced disease seems to be comparable to that of the older agents, bromocriptine and pergolide. Adverse effects can be reduced by starting the medication at a very low dose and then slowly titrating upward. Catechol-O-methyl transferase (COMT) inhibitors are indicated for the treatment of motor fluctuations in advanced disease, particularly the 'wearing-off' phenomenon. Tolcapone, a peripheral and central COMT inhibitor, appears to be quite effective, producing a 47% reduction in 'off' time. Unfortunately, 3 deaths have been observed, which are presumably secondary to tolcapone therapy. The drug has been withdrawn in many countries, and liver enzyme testing is mandatory in the US. Entacapone, a purely peripheral COMT inhibitor with a lower potency than tolcapone, has also proved to be effective and has not been associated with liver damage, obviating the need for testing.
近年来，帕金森病的治疗经历了大量研究，催生了多种新型药物。这在很大程度上是由于对长期左旋多巴治疗继发的运动并发症发展的不满所推动。根据帕金森病的阶段应用不同的治疗方法。在早期和轻度帕金森病中，司来吉兰有有限的症状缓解作用。其神经保护作用，尽管目前只是理论上的，但临床相关性存疑。有报道称司来吉兰与死亡率增加有关，尽管对5项不同试验的荟萃分析并不支持这一发现。新型非麦角碱多巴胺激动剂普拉克索和罗匹尼罗，已经进行了广泛研究以评估它们作为早期帕金森病单一疗法的疗效。这些新型激动剂是理想的初始症状性药物，主要是因为它们延迟了左旋多巴诱导的运动波动的发生。新型多巴胺激动剂在晚期疾病中的疗效似乎与 older agents，溴隐亭和培高利特相当。通过以非常低的剂量开始用药，然后缓慢向上滴定，可以减少不良反应。儿茶酚-O-甲基转移酶（COMT）抑制剂适用于治疗晚期疾病的运动波动，特别是“剂末现象”。托卡朋，一种外周和中枢COMT抑制剂，似乎相当有效，使“关”期时间减少47%。不幸的是，观察到3例死亡，推测可能继发于托卡朋治疗。该药物在许多国家已被撤回，在美国进行肝酶检测是强制性的。恩他卡朋，一种纯外周COMT抑制剂，效力低于托卡朋，也已被证明有效且与肝损伤无关，无需进行检测。
