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A brief history of levodopa.
J Neurol. 2010 Nov; 257(Suppl 2):S249-52.JN

Abstract

This article highlights some landmarks in the history of levodopa, beginning with its isolation in 1910-13 from seedlings of Vicia faba to the demonstration, in 1961, of its "miraculous" effect in patients with Parkinson's disease (PD). Midway between these two time points, in 1938, L: -dopa decarboxylase was discovered, the enzyme that produces dopamine (DA) from levodopa. In 1957, DA was shown to occur in the brain, and in 1959 it was found to be enriched in the basal ganglia. At that time the striatal localization of DA, together with studies done in 1957-58 in naive and reserpine-treated animals regarding DA in the brain and the central effects of levodopa, suggested its possible involvement in "extrapyramidal control" and "reserpine parkinsonism". Following these discoveries, a study of (postmortem) brains of patients with basal ganglia disorders, including PD, was started, demonstrating, in 1960, a severe striatal DA deficit specifically in PD, thus furnishing a rational basis for the concept of "DA replacement therapy" with levodopa. Accordingly, in 1961, the first highly successful clinical trial with i.v. levodopa was carried out. In 1963, the DA deficit in the PD substantia nigra was found, indicative of a nigrostriatal DA pathway in the human brain, subsequently established in animal studies in 1964-65. In 1967, the chronic, high dose oral levodopa regimen was introduced in treatment of PD. Besides the above highlights in the history of levodopa, the article also cites critical opinions of world authorities in brain research of the time, harmful to the cause of DA, levodopa and PD. Today, the concept of DA replacement with levodopa is uncontested, with levodopa being the "gold standard" of modern drug treatment of PD.

Authors+Show Affiliations

Center for Brain Research, Medical University of Vienna, Vienna, Austria.

Pub Type(s)

Historical Article
Journal Article
Review

Language

eng

PubMed ID

21080185

Citation

Hornykiewicz, Oleh. "A Brief History of Levodopa." Journal of Neurology, vol. 257, no. Suppl 2, 2010, pp. S249-52.
Hornykiewicz O. A brief history of levodopa. J Neurol. 2010;257(Suppl 2):S249-52.
Hornykiewicz, O. (2010). A brief history of levodopa. Journal of Neurology, 257(Suppl 2), S249-52. https://doi.org/10.1007/s00415-010-5741-y
Hornykiewicz O. A Brief History of Levodopa. J Neurol. 2010;257(Suppl 2):S249-52. PubMed PMID: 21080185.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A brief history of levodopa. A1 - Hornykiewicz,Oleh, PY - 2010/11/17/entrez PY - 2010/11/26/pubmed PY - 2011/10/4/medline SP - S249 EP - 52 JF - Journal of neurology JO - J Neurol VL - 257 IS - Suppl 2 N2 - This article highlights some landmarks in the history of levodopa, beginning with its isolation in 1910-13 from seedlings of Vicia faba to the demonstration, in 1961, of its "miraculous" effect in patients with Parkinson's disease (PD). Midway between these two time points, in 1938, L: -dopa decarboxylase was discovered, the enzyme that produces dopamine (DA) from levodopa. In 1957, DA was shown to occur in the brain, and in 1959 it was found to be enriched in the basal ganglia. At that time the striatal localization of DA, together with studies done in 1957-58 in naive and reserpine-treated animals regarding DA in the brain and the central effects of levodopa, suggested its possible involvement in "extrapyramidal control" and "reserpine parkinsonism". Following these discoveries, a study of (postmortem) brains of patients with basal ganglia disorders, including PD, was started, demonstrating, in 1960, a severe striatal DA deficit specifically in PD, thus furnishing a rational basis for the concept of "DA replacement therapy" with levodopa. Accordingly, in 1961, the first highly successful clinical trial with i.v. levodopa was carried out. In 1963, the DA deficit in the PD substantia nigra was found, indicative of a nigrostriatal DA pathway in the human brain, subsequently established in animal studies in 1964-65. In 1967, the chronic, high dose oral levodopa regimen was introduced in treatment of PD. Besides the above highlights in the history of levodopa, the article also cites critical opinions of world authorities in brain research of the time, harmful to the cause of DA, levodopa and PD. Today, the concept of DA replacement with levodopa is uncontested, with levodopa being the "gold standard" of modern drug treatment of PD. SN - 1432-1459 UR - https://www.unboundmedicine.com/medline/citation/21080185/A_brief_history_of_levodopa_ L2 - https://dx.doi.org/10.1007/s00415-010-5741-y DB - PRIME DP - Unbound Medicine ER -