Neuropharmacology of the adenosine A2a receptors

Studies done over the last 20 years have clearly shown that the adenosine A2A receptors are abundant in the striatum of several animal species. A2A receptors have also been found in the cerebral cortex and hippocampus. The distribution of A2A receptors closely matches that of dopamine D2 receptors, being expressed in striatopallidal GABAergic neurons that also express enkephalin. A variety of functional and behavioural studies have shown that antagonistic interactions exist between the A2A and D2 receptors. Thus, blockade of A2A receptors mimics the action of dopamine D2 receptor agonists. More recent studies have indicated that A2A receptors interact more broadly with dopaminergic pathways, D1 receptors are also involved in such interactions. Altogether, a variety of data support the suggestion that A2A receptor antagonists have a potential for treatment of Parkinson's disease, whereas A2A receptor agonists, which inhibit motor behaviour, may possess neuroleptic properties. Great progress is being made thanks to the development of potent and selective A2A receptor antagonists, notably the xanthines KF 17837 and CSC, and the non-xanthine heterocycle SCH 58261. These compounds and their radiolabelled forms make it possible to elucidate the role of brain A2A receptors further and open the way to the development of new agents for treatment of central nervous system disorders