Why target brain adenosine receptors? A historical perspective.

The quest for a non-dopaminergic approach to treating Parkinson's disease (PD) has been quietly progressing over the past several decades, and is now finding its momentum. Here, in what is more a memoir than a comprehensive review, we discuss work carried out over the past 50 years to show that adenosine acts as a critical signaling molecule via actions against a specific family of receptors. Importantly for PD, adenosine A receptors have a selective localization to the basal ganglia and specifically to the indirect output pathway, offering a targeted, non-dopaminergic opportunity to modulate basal ganglia output.