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Parkinson disease

Adjunctive entacapone therapy increases risk of dyskinesia

Nature Reviews Neurology volume 6, pages 590–591 (2010)Cite this article

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Levodopa treatment alleviates the motor symptoms that characterize Parkinson disease, but is associated with motor complications. Treatments that prolong the action of levodopa could potentially reduce the risk of these adverse events, but a new study reports that one such approach—entacapone as an adjunct to levodopa–carbidopa—is associated with earlier dyskinesia onset than with levodopa–carbidopa alone.

In Parkinson disease (PD), dopaminergic neurons in the brain selectively degenerate, and decreased dopamine levels are widely considered to be the cause of the motor symptoms that characterize this condition. Given that under normal physiological conditions dopaminergic neurons in the substantia nigra pars compacta fire continuously and, thus, maintain a relatively constant level of striatal dopamine,1 scientists and clinicians believe that continuous dopaminergic stimulation (CDS) of striatal dopamine receptors might be the optimal treatment for patients with PD. Treatments such as levodopa alleviate some of the motor symptoms of PD, but the use of this therapy can be associated with motor complications, including dyskinesia. How levodopa therapy causes these motor complications is unknown; however, the discontinuous nature of standard PD therapies might cause striatal dopamine receptors to be stimulated in a pulsatile manner, and this irregular delivery of dopamine to striatal neurons might cause the observed motor complications. In an animal model of PD, a treatment regimen designed to deliver dopamine in a relatively continuous manner was associated with a reduced risk of developing dyskinesia compared with standard treatment regimens.2 In a new study, however, Stocchi et al. have shown that levodopa–carbidopa and entacapone—an inhibitor of catechol-O-methyltransferase that increases the elimination half-life of levodopa—is associated with a reduced time to dyskinesia onset compared with levodopa–carbidopa alone in patients with PD.3

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Authors and Affiliations

  1. Neurological Clinical Research Unit, Institute of Molecular Medicine, University of Lisbon, Avenue Professor Egas Moniz, 1649–028, Lisbon, Portugal

    Cristina Sampaio

  2. Department of Neuroscience, Hospital de Santa Maria, University of Lisbon, Avenue Professor Egas Moniz, 1649–035, Lisbon, Portugal

    Joaquim J. Ferreira

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  1. Cristina Sampaio
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  2. Joaquim J. Ferreira
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Correspondence to Cristina Sampaio.

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Competing interests

J. J. Ferreira has acted as a consultant for and received honoraria for lectures from Lundbeck, Novartis and Teva Pharmaceuticals, he has also received research support from Lundbeck and Teva Pharmaceuticals. C. Sampaio declares no competing interests.

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Sampaio, C., Ferreira, J. Adjunctive entacapone therapy increases risk of dyskinesia. Nat Rev Neurol 6, 590–591 (2010). https://doi.org/10.1038/nrneurol.2010.158

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