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Review Article

Potential Therapeutic Applications of P2 Receptor Antagonists: From Bench to Clinical Trials

Author(s): Natiele C. da Silva Ferreira, Luiz A. Alves and Rômulo J. Soares-Bezerra*

Volume 20, Issue 9, 2019

Page: [919 - 937] Pages: 19

DOI: 10.2174/1389450120666190213095923

Price: $65

Abstract

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.

Keywords: P2X receptors, P2Y receptors, antagonists, therapy, thrombosis, pain, inflammation, clinical trials.

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Graphical Abstract

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