ABSTRACT
Cilostazol was selected from a number of analogs for further development because of its potent antiplatelet and vasodilatory activities and its minimal cardiac effects. Phosphodiesterase 3 (PDE3) inhibition was initially considered to be cilostazol’s sole mechanism of action. Studies have revealed inhibition of adenosine uptake to be another critical pharmacological action of cilostazol. Cilostazol is a selective and potent inhibitor of the PDE3 enzyme family that hydrolyzes cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate and is comprised of two subfamilies, PDE3A and phosphodiesterase 3B. Evidence that PDE3 inhibition plays an important role in the antithrombotic effect of cilostazol comes from the observations that cAMP levels in washed human and rabbit platelets were increased by cilostazol in a dose-dependent manner. The vasodilatory activity of cilostazol may contribute its therapeutic activity in intermittent claudication and other diseases. The vasodilatory effect of cilostazol has been explored in various pathological conditions.
