Repurposing an old drug for a new use: glybenclamide exerts antiplatelet activity by interacting with the thromboxane A(2) receptor. Academic Article uri icon

abstract

  • AIM: To investigate the potential antagonistic activity of the antidiabetic agent glybenclamide for the human platelet thromboxane A(2) receptor (abbreviated as TPR). METHODS: Platelets were obtained from healthy donors. Aggregation studies were performed in a model 700 aggregometry system. Radioactivity was counted in a Beckman LS 6000 liquid scintillation counter and calcium imaging was performed using an LS50B PerkinElmer Fluorescence Spectrometer. RESULTS: It was found that glybenclamide: 1) inhibited aggregation induced by the TPR agonist U46619 (IC(50)=2.3+/-0.31 micromol/L) and by the thromboxane A(2) precursor arachidonic acid (IC(50)=2.6+/-0.24 micromol/L); 2) displaced SQ29,548 from its binding sites on platelets; 3) lacked any detectable effects on aggregation stimulated by ADP, or the thrombin receptor activating-peptide 4; 4) blocked calcium mobilization induced by U46619, but not by ADP; and 5) failed to raise cAMP levels. CONCLUSION: The findings indicate that glybenclamide exerts inhibitory effects on platelets by interacting with TPR. Thus, glybenclamide or a rationally designed derivative has the potential to serve as an antithrombotic agent.

published proceedings

  • Acta Pharmacol Sin

author list (cited authors)

  • Ting, H. J., Murray, W. J., & Khasawneh, F. T.

citation count

  • 10

complete list of authors

  • Ting, Harold J||Murray, Wallace J||Khasawneh, Fadi T

publication date

  • January 2010