Levodopa therapy for Parkinson disease: A look backward and forward

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.