Therapeutic Potential of Highly Selective A3 Adenosine Receptor Ligands in the Central and Peripheral Nervous System.

Abstract

Ligands of the Gi protein-coupled adenosine A3 receptor (A3R) are receiving increasing interest as attractive therapeutic tools for the treatment of a number of pathological conditions of the central and peripheral nervous systems (CNS and PNS, respectively). Their safe pharmacological profiles emerging from clinical trials on different pathologies (e.g., rheumatoid arthritis, psoriasis and fatty liver diseases) confer a realistic translational potential to these compounds, thus encouraging the investigation of highly selective agonists and antagonists of A3R. The present review summarizes information on the effect of latest-generation A3R ligands, not yet available in commerce, obtained by using different in vitro and in vivo models of various PNS- or CNS-related disorders. This review places particular focus on brain ischemia insults and colitis, where the prototypical A3R agonist, Cl-IB-MECA, and antagonist, MRS1523, have been used in research studies as reference compounds to explore the effects of latest-generation ligands on this receptor. The advantages and weaknesses of these compounds in terms of therapeutic potential are discussed.

• Authors: Elisabetta Coppi, Federica Cherchi, Martina Venturini, Elena Lucarini, Renato Corradetti, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Felicita Pedata, Anna Maria Pugliese
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 27 Issue 6 (03 15 2022) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 35335254 (Publication Type: Journal Article, Review)

Chemical References

• Adenosine A3 Receptor Agonists
• Ligands
• Receptors, Purinergic P1

Topics

• Adenosine A3 Receptor Agonists (pharmacology, therapeutic use)
• Arthritis, Rheumatoid (drug therapy)
• Humans
• Ligands
• Peripheral Nervous System
• Receptors, Purinergic P1