Antiplatelet Effects of Selected Xanthine-Based Adenosine A2A and A2B Receptor Antagonists Determined in Rat Blood.

Abstract

The platelet aggregation inhibitory activity of selected xanthine-based adenosine A2A and A2B receptor antagonists was investigated, and attempts were made to explain the observed effects. The selective A2B receptor antagonist PSB-603 and the A2A receptor antagonist TB-42 inhibited platelet aggregation induced by collagen or ADP. In addition to adenosine receptor blockade, the compounds were found to act as moderately potent non-selective inhibitors of phosphodiesterases (PDEs). TB-42 showed the highest inhibitory activity against PDE3A along with moderate activity against PDE2A and PDE5A. The antiplatelet activity of PSB-603 and TB-42 may be due to inhibition of PDEs, which induces an increase in cAMP and/or cGMP concentrations in platelets. The xanthine-based adenosine receptor antagonists were found to be non-cytotoxic for platelets. Some of the compounds showed anti-oxidative properties reducing lipid peroxidation. These results may provide a basis for the future development of multi-target xanthine derivatives for the treatment of inflammation and atherosclerosis and the prevention of heart infarction and stroke.

• Authors: Monika Kubacka, Szczepan Mogilski, Marek Bednarski, Krzysztof Pociecha, Artur Świerczek, Noemi Nicosia, Jakub Schabikowski, Michał Załuski, Grażyna Chłoń-Rzepa, Jörg Hockemeyer, Christa E Müller, Katarzyna Kieć-Kononowicz, Magdalena Kotańska
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 24 Issue 17 (Aug 29 2023) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 37686188 (Publication Type: Journal Article)

Chemical References

• Xanthine
• diethylstilbestrol monophosphate
• Adenosine

Topics

• Animals
• Rats
• Xanthine (pharmacology)
• Blood Platelets
• Adenosine
• Atherosclerosis