Possible Interaction: Adenosine and Cilostazol

“Recent preclinical studies have demonstrated that CLZ also possesses the ability to inhibit adenosine uptake by various cells, a property that distinguishes CLZ from other PDE3 inhibitors, such as milrinone.”

“In the present studies, cilostazol inhibited [3H]-adenosine uptake in both platelets and erythrocytes with a … 7 &mgr;M. Next collagen-induced platelet aggregation was studied and it was found that adenosine (1 &mgr;M), having … the IC50 of cilostazol from 2.66 &mgr;M …;M (p < 0.01).”

“These data show that cilostazol , unlike milrinone, inhibits adenosine uptake, and thus potentiates adenosine accumulation from a 2-min ischemia.”

“ Cilostazol inhibits PDE III in platelets through an increase in adenosine 3 ́,5 ́-cyclic monophosphate (cAMP) content and activation of protein kinase A, resulting in antiplatelet aggregation.”

“Adding a low concentration of adenosine (0.3 microM) did not inhibit shear-induced platelet aggregation, but significantly enhanced the inhibitory effect of cilostazol in platelet-rich plasma.”

“ Cilostazol is classified as an antiplatelet agent because it inhibits the platelet aggregation induced by collagen, 5'-adenosine diphosphate ( ADP ), epinephrine, and arachidonic acid.”

“Papaverine, cilostazol , and rolipram also augmented both the magnitude and the duration of Isc following low dose stimulation of adenosine receptors with Ado (0.1-1.0 microM, P < 0.01).”

“ Cilostazol is a phosphodiesterase III inhibitor increases adenosine 3' , 5'-cyclic monophosphate (cyclic AMP) level which inhibits hepatic stellate cell activation.”

“ Cilostazol and draflazine increased the dialysate adenosine concentration during the first 10 min of muscle contraction, but had no effect during ischemia, most likely because of the high AMP deaminase activity in skeletal muscle.”

“In the cerebral arterioles, low concentration (10–6M) of cilostazol or milrinone caused a significant shift of the dose-vasodilatory response curve for adenosine to the left.”