NEUROPHARMACOLOGY OF THE ADENOSINE A(2A) RECEPTORS

Studies done over the last 20 years have clearly shown that the adenos ine A(2A) receptors are abundant in the striatum of several animal spe cies. A(2)A receptors have also been found in the cerebral cortex and hippocampus. The distribution of A(2A) receptors closely matches that of dopamine D-2 receptors, being expressed in striatopallidal GABAergi c neurons that also express enkephalin. A variety of functional and be havioural studies have shown that antagonistic interactions exist betw een the A(2A) and D-2 receptors. Thus, blockade of A(2)A receptors mim ics the action of dopamine D-2 receptor agonists. More recent studies have indicated that A(2)A receptors interact more broadly with dopamin ergic pathways, D-1 receptors are also involved in such interactions. Altogether, a variety of data support the suggestion that A(2A) recept or antagonists have a potential for treatment of Parkinson's disease, whereas A(2A) receptor agonists, which inhibit motor behaviour, may po ssess neuroleptic properties. Great progress is being made thanks to t he development of potent and selective A(2)A receptor antagonists, not ably the xanthines KF 17837 and CSC, and the non-xanthine heterocycle SCH 58261. These compounds and their radiolabelled forms make it possi ble to elucidate the role of brain A(2A) receptors further and open th e way to the development of new agents for treatment of central nervou s system disorders. (C) 1997 Wiley-Liss, Inc.