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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

A2A Adenosine Receptor Antagonists and their Potential in Neurological Disorders

Author(s): Catia Lambertucci, Gabriella Marucci, Daniela Catarzi, Vittoria Colotta, Beatrice Francucci, Andrea Spinaci, Flavia Varano and Rosaria Volpini*

Volume 29, Issue 28, 2022

Published on: 14 April, 2022

Page: [4780 - 4795] Pages: 16

DOI: 10.2174/0929867329666220218094501

Price: $65


Endogenous nucleoside adenosine modulates a number of physiological effects through interaction with P1 purinergic receptors. All of them are G protein-coupled receptors, and, to date, four subtypes have been characterized and named A1, A2A, A2B, and A3. In recent years, adenosine receptors, particularly the A2A subtype, have become attractive targets for the treatment of several neurodegenerative disorders, known to involve neuroinflammation, like Parkinson’s and Alzheimer’s diseases, multiple sclerosis, and neuropsychiatric conditions. In fact, it has been demonstrated that inhibition of A2A adenosine receptors exerts neuroprotective effects counteracting neuroinflammatory processes and astroglial and microglial activation. The A2A adenosine receptor antagonist istradefylline, developed by Kyowa Hakko Kirin Inc., was approved in Japan as adjunctive therapy for the treatment of Parkinson’s disease, and very recently, it was also approved by the US Food and Drug Administration. These findings pave the way for new therapeutic opportunities, so, in this review, a summary of the most relevant and promising A2A adenosine receptor antagonists will be presented along with their preclinical and clinical studies in neuroinflammation related diseases.

Keywords: A2A adenosine receptor, A2A adenosine receptor antagonists, neuroinflammation, neuroprotection, Parkinson’s disease, adenosine receptors, xanthine derivatives, non-xanthine derivatives.

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