Adenosine A2A receptor antagonist treatment of Parkinson’s disease

Abstract

Adenosine A2A receptors have a unique cellular and regional distribution in the basal ganglia (BG), being particularly concentrated in areas richly innervated by dopamine (DA) such as the caudateputamen, otherwise called striatum, and the globus pallidus. Adenosine A2A and DA D2 receptors are capable of forming functional heteromeric complexes and are colocalised in striatopallidal neurons. Based on the peculiar cellular and regional distribution of this receptor and in line with data showing that A2A receptor antagonists improve motor symptoms of Parkinson’s disease (PD) in animal models and in clinical trials, A2A receptor antagonists have emerged as an attractive nondopaminergic target to improve the motor deficits that characterise PD. Experimental data have also shown that A2A receptor antagonists are capable of exerting a neuroprotective effect and do not induce neuroplasticity phenomena that complicate long-term dopaminergic treatments. The present review will provide an updated summary of results reported in the literature concerning the biochemical characteristics and BG distribution of A2A receptors. We subsequently aim to examine the effects of adenosine A2A antagonists in rodent and primate models of PD and L-DOPA-induced dyskinesia. Finally, conclusive remarks will be made on the neuroprotective effects of A2A antagonists and on the translation of adenosine A2A receptor antagonists in the treatment of PD.