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Dual actions of A 2A adenosine receptor antagonists on motor dysfunction and neurodegenerative processes
Author(s) -
Ongini Ennio,
Monopoli Angela,
Impagnatiello Francesco,
Fredduzzi Silva,
Schwarzschild Michael,
Chen JiangFan
Publication year - 2001
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/ddr.1137
Subject(s) - neuroprotection , neuroscience , receptor , neurochemical , adenosine receptor , dopamine , pharmacology , dopamine receptor d2 , dopamine receptor , parkinson's disease , striatum , adenosine a2a receptor , medicine , psychology , biology , disease , agonist
Of the four known adenosine receptors, the A 2A receptor has received much attention over the last few years. The discovery of high‐affinity and selective A 2A adenosine receptor antagonists, together with the development of different genetic lines of mice lacking A 2A receptors, have greatly contributed to the new insights into the mechanisms whereby A 2A receptors modulate central nervous system functions. Efforts made using the prototypic A 2A receptor antagonists, e.g., the 8‐styrylxanthine KW 6002 and the pyrazolotriazolopyrimidine SCH 58261, have shown that these drugs are effective in different models of motor impairment mimicking the main features of Parkinson’s disease. Moreover, these drugs show neuroprotective properties in models of brain injury. Consistent with pharmacology, A 2A receptor knockout mice have been found to be less sensitive to both motor impairment and neurochemical changes relevant to neurodegenerative disorders. The main effect of A 2A receptor blockade or inactivation is related to selective interaction with dopamine‐mediated function in the striatum. However, there are responses which appear to be independent of dopamine receptors while the mechanisms underlying neuroprotection remain to be elucidated. Overall, there are now compounds that appear to be promising for treatment of Parkinson’s disease and related neurodegenerative disorders. The efforts currently ongoing to understand their efficacy in patients will make it possible to assess whether A 2A receptor blockers are a new interesting class of antiparkinsonian agents. Drug Dev. Res. 52:379–386, 2001. © 2001 Wiley‐Liss, Inc.