Adenosine receptors in neurological disorders

Adenosine is present in the extacellular space of organs and tissues in the mammalian organism where it modulates a variety of physiological processes through specific cell membrane receptors which have been identified as members of the G-protein coupled receptors (GPCRs). Currently, four receptors have been cloned and characterised, namely A1, A2A, A2B, A3 adenosine receptors. The different distribution of receptor populations in organs and tissues together with their importance in normal and altered conditions make each individual adenosine receptor an attractive target for the discovery of new pharmacological agents. Major efforts have involved the A1 and A2A receptors with the central nervous (and cardiovascular) systems being the medical areas of highest interest. Thus, a variety of selective receptor agonists and antagonists have been discovered and some are currently under development for the treatment of neurological disorders. Treatment of pain, neurodegenerative diseases, such as Parkinson's (PD) and Huntington's disease (HD), cognitive impairment and epilepsy are all potential therapy areas of future drug development. This review describes the scientific background information currently available together with the rationale underlying the innovative strategies associated with the modulation of each individual adenosine receptor.