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Neuropharmacology of the adenosine A 2A receptors
Author(s) -
Ongini Ennio,
Dionisotti Silvio,
Morelli Micaela,
Ferré Sergi,
Svenningsson Per,
Fuxe Kjell,
Fredholm Bertil B.
Publication year - 1996
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/(sici)1098-2299(199611/12)39:3/4<450::aid-ddr27>3.0.co;2-3
Subject(s) - adenosine a2a receptor , receptor , neuroscience , dopamine receptor d2 , neuropharmacology , dopamine , dopaminergic , biology , adenosine receptor , pharmacology , chemistry , agonist , biochemistry
Studies done over the last 20 years have clearly shown that the adenosine A 2A receptors are abundant in the striatum of several animal species. A 2A 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 GABAergic neurons that also express enkephalin. A variety of functional and behavioural studies have shown that antagonistic interactions exist between the A 2A and D 2 receptors. Thus, blockade of A 2A receptors mimics the action of dopamine D 2 receptor agonists. More recent studies have indicated that A 2A receptors interact more broadly with dopaminergic pathways, D 1 receptors are also involved in such interactions. Altogether, a variety of data support the suggestion that A 2A receptor antagonists have a potential for treatment of Parkinson's disease, whereas A 2A receptor agonists, which inhibit motor behaviour, may possess neuroleptic properties. Great progress is being made thanks to the development of potent and selective A 2A 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 A 2A receptors further and open the way to the development of new agents for treatment of central nervous system disorders. Drug Dev. Res. 39:450–460, 1996. © 1997 Wiley‐Liss, Inc.