Inhibition of shear stress-induced platelet aggregation by cilostazol, a specific inhibitor of cGMP-inhibited phosphodiesterase, in vitro and ex vivo

Cilostazol(6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)-butoxy]-3,4-dihydro-2(1H)-quinolinone) selectively inhibits cGMP-inhibited phosphodiesterase(PDE3) and is a potent inhibitor of platelet aggregation induced by various agonists. Effect of cilostazol on shear stress-induced human platelet aggregation(SIPA) was examined in vitro and ex vivo. Cilostazol inhibited SIPA dose-dependently in vitro. The IC50 value of cilostazol for inhibition of SIPA was 15 +/- 2.6 mu M(m +/- SE, n=5), which was very similar to that(12.5 +/- 2.1 mu M) for inhibition of ADP-induced platelet aggregation. Cilostazol potentiates the inhibition of SIPA by PGE(1) and enhances its ability to increase cAMP concentrations. A single oral adminstration of 100 mg cilostazol to healthy volunteers produced a significant inhibition of SIPA. This study demonstrates that cilostazol is an effective inhibitor of SIPA, which may be important for the prevention and the treatment of arterial occlusive diseases. (C) 1997 Elsevier Science Inc.