Title:A2A Adenosine Receptor Antagonists as Therapeutic Candidates: Are They Still an Interesting Challenge?
Volume: 18
Issue: 14
Author(s): Barbara Cacciari*, Giampiero Spalluto and Stephanie Federico
Affiliation:
- Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara, Via Fossato di Mortara 17-19, I-44121 Ferrara,Italy
Keywords:
A2A antagonists, adenosine, Parkinson’s disease, cancer, heterotetramers, immunosuppression.
Abstract: In the past decades, many efforts were undertaken to develop ligands for the adenosine receptors,
with the purpose to individuate agonists and antagonists affinity and selectivity for each subtypes,
namely A1, A2A, A2B, and A3. These intense studies allowed a deeper knowledge of the nature
and, moreover, of the pathophysiological roles of all the adenosine receptor subtypes. In particular, the
involvement of the A2A adenosine receptor subtype in some physiological mechanisms in the brain,
that could be related to important diseases such as the Parkinson’s disease, encouraged the research in
this field. Particular attention was given to the antagonists endowed with high affinity and selectivity
since they could have a real employment in the treatment of Parkinson’s disease, and some compounds,
such as istradefylline, preladenant and tozadenant, are already studied in clinical trials. Actually,
the role of A2A antagonists in Parkinson’s disease is becoming contradictory due to contrasting
results in the last studies, but, at the same time, new possible employments are emerging for this class
of antagonists in cancer pathologies as much interesting to legitimate further efforts in the research of
A2A ligands.