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Levodopa—toxic or neuroprotective?

Nature Clinical Practice Neurology volume 2, pages 518–519 (2006)Cite this article

The successful administration of levodopa in the treatment of Parkinson's disease in 1967 was nothing short of miraculous.1 Early morning news shows of the time ran film clips of pre-treatment wheelchair-bound patients playing baseball after treatment with levodopa. My own introduction to clinical trials under the mentorship of Harold L Klawans was forever shaped by the experience of transforming patients' lives with the introduction of an experimental agent—a far cry from all of our recent work in which an army of statisticians and huge numbers of research subjects are required to demonstrate significance.

In the early 1990s, however, two distinct but gradually interwoven lines of inquiry led to concern that levodopa could be harmful to patients. First, a wide range of laboratory experiments demonstrated levodopa toxicity. Second, the association of motor fluctuations and dyskinesias with chronic dopaminergic treatment of patients with Parkinson's disease was transformed from an adverse effect to a 'toxic' effect of levodopa. How these lines of inquiry became intermixed, leading to the hypothesis that levodopa is toxic in this patient population, is highly instructive to our understanding of theory, hypothesis, fact and practice in Parkinson's disease. What was the evidence for toxicity, how did such views gain wide publicity, and what can we learn from this strange interlude of so-called levodopa toxicity?

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Authors and Affiliations

  1. Professor and Chairman of the Department of Neurology at the University of Maryland School of Medicine and Director of the Maryland Parkinson's Disease and Movement Disorders Center, Baltimore, MD, USA

    William J Weiner

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  1. William J Weiner
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Correspondence to William J Weiner.

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Weiner, W. Levodopa—toxic or neuroprotective?. Nat Rev Neurol 2, 518–519 (2006). https://doi.org/10.1038/ncpneuro0293

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