Cilostazol and dipyridamole synergistically inhibit human platelet aggregation

Journal of Cardiovascular Pharmacology
Yongge LiuBing Sun

Abstract

It has been previously shown that cilostazol (Pletal), a drug for relief of symptoms of intermittent claudication, potently inhibits cyclic nucleotide phosphodiesterase type 3 (PDE3) and moderately inhibits adenosine uptake. It elevates extracellular adenosine concentration, by inhibiting adenosine uptake, and combines with PDE3 inhibition to augment inhibition of platelet aggregation and vasodilation while attenuating positive chronotropic and inotropic effects on the heart. In the present study, we tested the hypothesis that cilostazol combined with a more potent adenosine uptake inhibitor, dipyridamole, synergistically inhibited platelet aggregation in human blood. In the presence of exogenous adenosine (1 microM), the combination of cilostazol and dipyridamole synergistically increased intra-platelet cAMP. Furthermore, cilostazol inhibited platelet aggregation in a washed platelet assay concentration-dependently with IC50s of 0.17 +/- 0.04 microM (P < 0.05 versus plus adenosine alone of 0.38 +/- 0.05 microM), 0.11 +/- 0.06 microM (P < 0.05), and 0.01 +/- 0.01 microM (P < 0.005) when combined with 1, 3, or 10 microM dipyridamole, respectively (n = 5). In whole blood, cilostazol (0.3 to 3 microM) and dipyridamole (1 or 3 micr...Continue Reading

References

May 1, 1994·British Journal of Pharmacology·M BöhmE Erdmann
Sep 1, 1995·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Y Kimura
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Sep 28, 2002·Journal of Cardiovascular Pharmacology·Bing SunJun-Ichi Kambayashi
Oct 8, 2003·Current Pharmaceutical Design·Junichi KambayashiFrank Czerwiec

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Citations

Dec 8, 2009·Circulation Journal : Official Journal of the Japanese Circulation Society·Miranda FongYongge Liu
Apr 24, 2013·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Shunichi SaitoShinji Uemoto
Aug 20, 2011·European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery·A HoriK Komori
Jun 30, 2019·Current Cardiology Reports·Ajay Nair SharmaAilin Barseghian
Apr 17, 2021·Cardiovascular Drugs and Therapy·Riyad Y KherallahYochai Birnbaum

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