Table of Contents Author Guidelines Submit a Manuscript
Parkinson’s Disease
Volume 2012, Article ID 489853, 8 pages
http://dx.doi.org/10.1155/2012/489853
Review Article

Receptor Antagonism and Dyskinesia in Parkinson’s Disease

1Department of Biomedical Sciences, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy
2CNR Institute of Neuroscience, 09042 Cagliari, Italy
3Interdepartmental Research Center for Parkinson’s Disease, National Neurological Institute C. Mondino, 27100 Pavia, Italy
4Department of Neurology, University of South Florida, Tampa, FL 33613, USA

Received 21 February 2012; Accepted 26 April 2012

Academic Editor: Anna Rosa Carta

Copyright © 2012 Micaela Morelli et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Dyskinesia, a major complication of treatment of Parkinson’s disease (PD), involves two phases: induction, which is responsible for dyskinesia onset, and expression, which underlies its clinical manifestation. The unique cellular and regional distribution of adenosine receptors in basal ganglia areas that are richly innervated by dopamine, and their antagonistic role towards dopamine receptor stimulation, have positioned receptor antagonists as an attractive nondopaminergic target to improve the motor deficits that characterize PD. In this paper, we describe the biochemical characteristics of receptors and the effects of adenosine antagonists in rodent and primate models of PD on L-DOPA-induced dyskinesia, together with relevant biomarker studies. We also review clinical trials of antagonists as adjuncts to L-DOPA in PD patients with motor fluctuations. These studies have generally demonstrated that the addition of an antagonist to a stable L-DOPA regimen reduces OFF time and mildly increases dyskinesia. However, limited clinical data suggest that the addition of an antagonist along with a reduction of L-DOPA might maintain anti-Parkinsonian benefit and reduce dyskinesia. Whether antagonists might reduce the development of dyskinesia has not yet been tested clinically.