This review considers the question of whether or not levodopa (l-dopa) is toxic in Parkinson’s disease. L-Dopa is often considered to be the most effective symptomatic treatment for Parkinson’s disease; however, there has been a longstanding concern that l-dopa might be toxic and accelerate neuronal degeneration as a consequence of reactive oxygen species generated by the drug’s oxidative metabolism. In vitro, l-dopa can induce degeneration of dopaminergic neurons, but it is not clear that the effects of the drug on cultured dopamine neurons reflect what happens in vivo. Clinical trials have tested the effect of l-dopa on clinical progression and have not demonstrated any findings indicative of toxicity. However, the author argues that symptomatic and long-duration effects of the drug could mask ongoing neuronal degeneration. For example, l-dopa induces a greater decline in imaging measures of dopaminergic function than placebo or dopamine agonists, consistent with toxicity. The author points out the need for further studies and recommends that l-dopa should be used at the lowest dose that provides satisfactory clinical control.
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Olanow CW: Levodopa: Effect on cell death and the natural history of Parkinson’s disease. Mov. Disord. 30(1): 37-44 (2015).
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http://www.ncbi.nlm.nih.gov/pubmed/25502620