Objective: This study aims to relook the journey of levodopa in the treatment of Parkinson’s disease.

Background: Levodopa has been used in the treatment of Parkinson’s disease for more than 50 years. Many new modalities of treatment have emerged, but still levodopa is the most important medication used in Parkinson’s disease.

Method: A Pubmed search was done on 31st January 2022, using keywords, [History of Levodopa], [History of carbidopa], [History of dopamine], [Arvid Carlson], [Oleh Hornykiewicz], and [George Cotzias]. Out of a total of 3441 articles, the final reference was based on the relevance of the review.

Results: The earliest description of dopaminergic treatment is reported in ancient Indian literature by Atmagupta, who used a powdered form of mucuna pruriens (Fabaceae) in treating tremors. In 1913, Levodopa was isolated from Vicia Faba, and later the discovery of dopa-decarboxylase, proved it to be a precursor of dopamine. Dopamine was first isolated in 1950 by Goodall, but its pharmacological role in the treatment of akinesia was established following Arvid Carlson’s experiment on Reserpine. Oleh Hornykiewicz, proved dopamine depletion in basal ganglia, in Parkinson’s disease brains. In 1961 while working with Birkmayer, Hornykiewicz reported that administration of Levodopa improved motor symptoms in 20 patients with Parkinson’s disease. The ‘high oral dose’ of the Levodopa regime was first introduced by George Cotzias, in 1967. After the therapeutic uses, many side effects of Levodopa were reported including postural hypotension, vomiting, and dyskinesias. Considering its major side effects on the gastrointestinal system, co-administration with carbidopa was recommended which helped in stopping the peripheral conversion of Levodopa and minimizing the adverse effects. In the next few years availability of sustained-release formulations of Levodopa and catechol-O-methyltransferase inhibitors helped in the wearing-off phenomenon seen in patients receiving long-term Levodopa treatment. In the last few decades, several advances have been made in the drug delivery mechanism of Levodopa including skin patches, and duodopa infusion.

Conclusion: Since its discovery, Levodopa has remained the mainstay in the treatment of Parkinson’s disease. The therapeutic success of Levodopa in the treatment of Parkinson’s disease reflects the importance of translational research where findings from basic research can be successfully utilized for clinical uses.

References: 1. Ovallath S, Sulthana B. Levodopa: History and therapeutic applications. Ann Indian Acad Neurol 2017;20:185-9.
2. Abbott, A. Levodopa: the story so far. Nature 466, S6–S7 (2010).
3. Hornykiewicz O. 50 years of levodopa. Mov Disord. 2015 Jun;30(7):1008. doi: 10.1002/mds.26240. Epub 2015 May 21. PMID: 25999218.
4. Fahn, S. (2008), The history of dopamine and levodopa in the treatment of Parkinson’s disease. Mov. Disord., 23: S497-S508.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-journey-of-levodopa-treatment-in-parkinsons-disease/