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History and Perspectives of A 2A Adenosine Receptor Antagonists as Potential Therapeutic Agents
Author(s) -
Preti Delia,
Baraldi Pier Giovanni,
Moorman Allan R.,
Borea Pier Andrea,
Varani Katia
Publication year - 2015
Publication title -
medicinal research reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.868
H-Index - 130
eISSN - 1098-1128
pISSN - 0198-6325
DOI - 10.1002/med.21344
Subject(s) - adenosine , adenosine a2a receptor , regulator , adenosine receptor , pharmacology , nucleoside , receptor , signal transduction , monoamine oxidase , neuroscience , pathogenesis , purine , biology , medicine , biochemistry , immunology , enzyme , gene , agonist
Growing evidence emphasizes that the purine nucleoside adenosine plays an active role as a local regulator in different pathologies. Adenosine is a ubiquitous nucleoside involved in various physiological and pathological functions by stimulating A 1 , A 2A , A 2B , and A 3 adenosine receptors (ARs). At the present time, the role of A 2A ARs is well known in physiological conditions and in a variety of pathologies, including inflammatory tissue damage and neurodegenerative disorders. In particular, the use of selective A 2A antagonists has been reported to be potentially useful in the treatment of Parkinson's disease (PD). In this review, A 2A AR signal transduction pathways, together with an analysis of the structure–activity relationships of A 2A antagonists, and their corresponding pharmacological roles and therapeutic potential have been presented. The initial results from an emerging polypharmacological approach are also analyzed. This approach is based on the optimization of the affinity and/or functional activity of the examined compounds toward multiple targets, such as A 1 /A 2A ARs and monoamine oxidase‐B (MAO‐B), both closely implicated in the pathogenesis of PD.