Levodopa

K K Jain MD (Dr. Jain is a consultant in neurology and has no relevant financial relationships to disclose.)
Originally released December 18, 1998; last updated April 17, 2017; expires April 17, 2020

This article includes discussion of levodopa, dopa, dihydroxyphenylalanine, and L-dopa. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Since its introduction into clinical use for Parkinson disease more than half a century ago, levodopa, a precursor of dopamine, remains the gold standard. It is used in combination with carbidopa, and various preparations are being developed to enhance its bioavailability as well as improve its delivery for reducing complications due to plasma level fluctuations. This article reviews the pharmacology, recent clinical trials, and adverse effects of levodopa. Several movement disorders can occur as adverse effects of levodopa therapy, eg, choreoathetosis, dystonia, akathisia, myoclonus, tremor, and dyskinesias.

Key points

 

• Levodopa is a precursor for dopamine, and its anti–Parkinson disease effects are mediated by the synthesis of dopamine, which subsequently interacts with dopamine receptors.

 

• More than half a century after its introduction into clinical use, levodopa remains the gold standard for the treatment of Parkinson disease.

 

• To overcome the short half-life of levodopa, it is usually combined with the decarboxylase inhibitor, carbidopa, and various preparations are being developed to enhance its bioavailability as well as improve its delivery for reducing complications due to plasma level fluctuations.

 

• Several movement disorders can occur as adverse effects of levodopa therapy, eg, choreoathetosis, dystonia, akathisia, myoclonus, tremor, and dyskinesias.

 

• Levodopa-induced dyskinesias are problematic, and to prevent peak dose dyskinesias, levodopa concentrations should be steadily maintained in the therapeutic range.

Historical note and terminology

Levodopa was demonstrated in nature, and a simplified manufacturing process was described in 1913 (Guggenheim 1913). Experimental studies in the 1950s showed that levodopa could reverse reserpine-induced akinesia in rabbits, but the biochemical basis of this action was not clear until Carlsson demonstrated that dopamine in the brain was depleted with reserpine and could be restored with levodopa (Carlsson 1959). In 1961 Birkmayer and Hornykiewicz showed that intravenous dopa briefly improved symptoms in patients with Parkinson disease (Birkmayer and Hornykiewicz 1961). Seven years later, Cotzias showed the effectiveness of levodopa for Parkinson disease by clinical trial (Cotzias 1968). Since its introduction into the clinical use in the early 1970s, levodopa remains the single most effective treatment for Parkinson disease. Stable and controlled formulations that ensure clinical response need to be developed to reduce the undesirable effects that restrict its efficacy (Pezzoli and Zini 2010). More than half a century after its introduction into clinical practice, levodopa remains the gold standard for treatment of Parkinson disease.

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