Background: Extracellular purines and pyrimidines have important physiological functions
in mammals. Purines and pyrimidines act on P1 and P2 purinergic receptors, which are widely expressed
in the plasma membrane in various cell types. P2 receptors act as important therapeutic targets
and are associated with several disorders, such as pain, neurodegeneration, cancer, inflammation, and
thrombosis. However, the use of antagonists for P2 receptors in clinical therapy, with the exception of
P2Y12, is a great challenge. Currently, many research groups and pharmaceutical companies are
working on the development of specific antagonist molecules for each receptor subtype that could be
used as new medicines to treat their respective disorders.
Objective: The present review compiles some interesting findings on the application of P2 receptor antagonists
in different in vitro and in vivo experimental models as well as the progress of advanced
clinical trials with these compounds.
Conclusion: Despite all of the exciting results obtained on the bench, few antagonists of P2 receptors
advanced to the clinical trials, and once they reach this stage, the effectiveness of the therapy is not
guaranteed, as in the example of P2X7 antagonists. Despite this, P2Y12 receptor antagonists have a
history of success and have been used in therapy for at least two decades to prevent thrombosis in patients
at risk for myocardial infarctions. This breakthrough is the motivation for scientists to develop
new drugs with antagonistic activity for the other P2 receptors; thus, in a matter of years, we will have
an evolution in the field of purinergic therapy.