Potential Therapeutic Relevance of Adenosine A2B and A2A Receptors in the Central Nervous System

Adenosine A(2B) and, much more importantly, adenosine A(2A) receptors modulate many physiological and pathological processes in the brain. In this review, the most recent evidence concerning the role of such receptors and their potential therapeutic relevance is discussed. The low affinity of A(2B) receptors for adenosine implies that they might represent a good therapeutic target, since they are activated only under pathological conditions (when adenosine levels raise up to micromolar concentrations). The availability of selective ligands for A(2B) receptors would allow exploration of such an hypothesis. Since adenosine A(2A) receptors mediate both potentially neuroprotective and potentially neurotoxic effects, their role in neurodegenerative diseases is highly controversial. Nevertheless, A(2A) receptor antagonists have shown clear antiparkinsonian effects, and a great interest exists on the role of A(2A) receptors in Alzheimer's disease, brain ischaemia, spinal cord injury, drug addiction and other conditions. In order to establish whether such receptors represent a target for CNS diseases, at least two conditions are needed: the full comprehension of A(2A)-dependent mechanisms and the availability of ligands capable of discriminating among the different receptor populations.