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Review
. 2010 Sep 7:5:229-38.
doi: 10.2147/cia.s6456.

Levodopa in the treatment of Parkinson's disease: an old drug still going strong

Werner Poewe  1 , Angelo Antonini, Jan Cm Zijlmans, Pierre R Burkhard, François Vingerhoets
Affiliations
Review

Levodopa in the treatment of Parkinson's disease: an old drug still going strong

Werner Poewe et al. Clin Interv Aging. .

Abstract

After more than 40 years of clinical use, levodopa (LD) remains the gold standard of symptomatic efficacy in the drug treatment of Parkinson's disease (PD). Compared with other available dopaminergic therapies, dopamine replacement with LD is associated with the greatest improvement in motor function. Long-term treatment with LD is, however, often complicated by the development of various types of motor response oscillations over the day, as well as drug-induced dyskinesias. Motor fluctuations can be improved by the addition of drugs such as entacapone or monoamine oxidase inhibitors, which extend the half-life of levodopa or dopamine, respectively. However, dyskinesia control still represents a major challenge. As a result, many neurologists have become cautious when prescribing therapy with LD. This review summarizes the available evidence regarding the use of LD to treat PD and will also address the issue of LD delivery as a critical factor for the drug's propensity to induce motor complications.

Keywords: Parkinson’s disease; dyskinesia; levodopa; motor fluctuations.

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Figures

Figure 1
Figure 1
Mean ± standard deviation change from baseline in A) Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores during the course of the five-year 056 and four-year comparison of the CALM-PD (Comparison of Agonist Pramipexole versus Levodopa on Motor Complications of Parkinson’s Disease) trials by treatment assignment. B) Percentage of patients receiving monotherapy with dopamine agonists requiring levodopa supplementation after two and four years of treatment.
Figure 2
Figure 2
Comparison of the risk of motor complications and other adverse events associated with levodopa versus dopamine agonists. The length of the arrow reflects the extent of risk. Note: *Ergot-derived dopamine agonists compared with levodopa.
Figure 3
Figure 3
Oral levodopa therapy – hurdles on the route from the mouth to the brain. A number of factors impact on the progress of levodopa from the time of ingestion until it reaches the brain and is converted to dopamine. Abbreviations: AADC, amino acid decarboxylase; COMT, catechol-O-methyl transferase.
Figure 4
Figure 4
The evolution of levodopa-associated motor fluctuations. A comparison of plasma levodopa levels, brain dopamine levels, and the resulting motor response in early and advanced stages of Parkinson’s disease is shown. Abbreviation: SN, substantia nigra.
See this image and copyright information in PMC

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