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

Abstract

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 microM (m +/- SE, n=5), which was very similar to that (12.5 +/- 2.1 microM) for inhibition of ADP-induced platelet aggregation. Cilostazol potentiates the inhibition of SIPA by PGE1 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.

• Authors: N Minami, Y Suzuki, M Yamamoto, H Kihira, E Imai, H Wada, Y Kimura, Y Ikeda, H Shiku, M Nishikawa
• Journal: Life sciences (Life Sci) Vol. 61 Issue 25 Pg. PL 383-9 ( 1997) ISSN: 0024-3205 [Print] Netherlands
• PMID: 9416770 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Platelet Aggregation Inhibitors
• Tetrazoles
• Cyclic AMP
• 3',5'-Cyclic-AMP Phosphodiesterases
• Cyclic Nucleotide Phosphodiesterases, Type 3
• Cilostazol

Topics

• 3',5'-Cyclic-AMP Phosphodiesterases (antagonists & inhibitors)
• Administration, Oral
• Adult
• Blood Platelets (drug effects, metabolism)
• Cilostazol
• Cyclic AMP (metabolism)
• Cyclic Nucleotide Phosphodiesterases, Type 3
• Enzyme Inhibitors (blood, pharmacokinetics, pharmacology)
• Humans
• Male
• Platelet Aggregation Inhibitors (blood, pharmacokinetics, pharmacology)
• Stress, Mechanical
• Tetrazoles (blood, pharmacokinetics, pharmacology)