Title:A2A Adenosine Receptor Antagonists and their Potential in Neurological
Disorders
Volume: 29
Issue: 28
Author(s): Catia Lambertucci, Gabriella Marucci, Daniela Catarzi, Vittoria Colotta, Beatrice Francucci, Andrea Spinaci, Flavia Varano and Rosaria Volpini*
Affiliation:
- Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, 62032 Camerino (MC), Italy
Keywords:
A2A adenosine receptor, A2A adenosine receptor antagonists, neuroinflammation, neuroprotection, Parkinson’s disease, adenosine receptors, xanthine derivatives, non-xanthine derivatives.
Abstract: 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.