LeWitt Peter A, Fahn Stanley
From the Department of Neurology (P.A.L.), Henry Ford Hospital; Department of Neurology (P.A.L.), Wayne State University School of Medicine, Detroit, MI; and Department of Neurology (S.F.), Columbia University Medical Center, New York, NY.
Neurology. 2016 Apr 5;86(14 Suppl 1):S3-12. doi: 10.1212/WNL.0000000000002509. Epub 2016 Apr 4.
Although levodopa is widely recognized as the most effective therapy for Parkinson disease (PD), its introduction 5 decades ago was preceded by several years of uncertainty and equivocal clinical results. The translation of basic neuroscience research by Arvid Carlsson and Oleh Hornykiewicz provided a logical pathway for treating PD with levodopa. Yet the pioneering clinicians who transformed PD therapeutics with this drug--among them Walther Birkmayer, Isamu Sano, Patrick McGeer, George Cotzias, Melvin Yahr, and others--faced many challenges in determining whether the concept and the method for replenishing deficient striatal dopamine was correct. This article reviews highlights in the early development of levodopa therapy. In addition, it provides an overview of emerging drug delivery strategies that show promise for improving levodopa's pharmacologic limitations.
尽管左旋多巴被广泛认为是治疗帕金森病（PD）最有效的疗法，但在50年前它被引入之前，曾有过数年的不确定性和不明确的临床结果。阿尔维德·卡尔森（Arvid Carlsson）和奥莱赫·霍尔尼基维茨（Oleh Hornykiewicz）的基础神经科学研究转化为用左旋多巴治疗PD提供了一条合乎逻辑的途径。然而，用这种药物改变PD治疗方法的先驱临床医生——包括瓦尔特·比尔克迈尔（Walther Birkmayer）、佐野勇（Isamu Sano）、帕特里克·麦吉尔（Patrick McGeer）、乔治·科齐亚斯（George Cotzias）、梅尔文·亚尔（Melvin Yahr）等人——在确定补充纹状体多巴胺不足的概念和方法是否正确方面面临许多挑战。本文回顾了左旋多巴治疗早期发展的要点。此外，还概述了新兴的药物递送策略，这些策略有望改善左旋多巴的药理学局限性。
