A2A Receptor Antagonism and Dyskinesia in Parkinson's Disease. (17th June 2012)

• Record Type: Journal Article
• Authors: Morelli, Micaela; Blandini, Fabio; Simola, Nicola; Hauser, Robert A.
• Other Names: Carta Anna Rosa Academic Editor.
• Is Part Of: Parkinson's disease. Volume 2012(2012)
• Publication Date: 2012-06-17
• Subjects: Parkinson's disease -- Periodicals; Parkinson's disease -- Treatment -- Periodicals; 616.833005
• DOI: 10.1155/2012/489853
• Languages: English
• ISSNs: 2090-8083

Abstract

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 A 2A receptors in basal ganglia areas that are richly innervated by dopamine, and their antagonistic role towards dopamine receptor stimulation, have positioned A 2A receptor antagonists as an attractive nondopaminergic target to improve the motor deficits that characterize PD. In this paper, we describe the biochemical characteristics of A 2A receptors and the effects of adenosine A 2A antagonists in rodent and primate models of PD on L-DOPA-induced dyskinesia, together with relevant biomarker studies. We also review clinical trials of A 2A antagonists as adjuncts to L-DOPA in PD patients with motor fluctuations. These studies have generally demonstrated that the addition of an A 2A antagonist to a stable L-DOPA regimen reduces OFF time and mildly increases dyskinesia. However, limited clinical data suggest that the addition of an A 2A antagonist along with a reduction of L-DOPA might maintain anti-Parkinsonian benefit and reduce dyskinesia. Whether A 2A antagonists might reduce the development of dyskinesia has not yet been tested clinically.