Hagan J J, Middlemiss D N, Sharpe P C, Poste G H
SmithKline Beecham Pharmaceuticals, Harlow, UK.
Trends Pharmacol Sci. 1997 May;18(5):156-63. doi: 10.1016/s0165-6147(97)01050-x.
L-Dopa has long been the mainstay of therapy for Parkinson's disease but its long-term shortcomings, principally uncoordinated, spasmodic or irregular movements (dyskinesias) and fluctuating control of motor symptoms (on/off fluctuations), are well documented. The postulated neuroprotective properties of L-deprenyl, often used as an adjunct to L-dopa, are under scrutiny and doubts have also been raised regarding its safety. Alternative therapeutic approaches are clearly needed. In this review, Jim Hagan, Derek Middlemiss, Paul Sharpe and George Poste outline some new approaches to treatment, with an emphasis on novel, selective dopamine receptor agonists. In addition, Parkinson's disease is commonly thought to be caused by the neurotoxic effects of an unidentified agent but recent data indicate a greater genetic component than previously recognized. Developments in the genetics of Parkinson's disease may provide the key to the next generation of therapeutics.
左旋多巴长期以来一直是帕金森病治疗的主要药物，但其长期存在的缺点，主要是不协调、痉挛性或不规则运动（异动症）以及运动症状控制波动（开/关波动），已有充分记录。通常作为左旋多巴辅助药物使用的L-司来吉兰的假定神经保护特性正在接受审查，人们也对其安全性提出了质疑。显然需要其他治疗方法。在这篇综述中，吉姆·哈根、德里克·米德米斯、保罗·夏普和乔治·波斯特概述了一些新的治疗方法，重点是新型、选择性多巴胺受体激动剂。此外，帕金森病通常被认为是由一种不明物质的神经毒性作用引起的，但最近的数据表明其遗传因素比以前认识到的更为重要。帕金森病遗传学的发展可能为下一代治疗方法提供关键。
