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Current Pharmaceutical Design

Eiditor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Cilostazol as a Unique Antithrombotic Agent

Author(s): Junichi Kambayashi, Yongge Liu, Bing Sun, Yasmin Shakur, Masuhiro Yoshitake and Frank Czerwiec

Volume 9 , Issue 28 , 2003

Page: [2289 - 2302] Pages: 14

DOI: 10.2174/1381612033453910

Price: $58

Abstract

Cilostazol (CLZ) was originally developed as a selective inhibitor of cyclic nucleotide phosphodiesterase 3 (PDE3). PDE3 inhibition in platelets and vascular smooth muscle cells (VSMC) was expected to provide an antiplatelet effect and vasodilation. 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. After extensive preclinical and clinical studies, CLZ has been shown to have unique antithrombotic and vasodilatory properties based upon these novel mechanisms of action. CLZ was approved in 1988 for the treatment of symptoms related to peripheral arterial occlusive disease in Japan (Pletaal®) and in 1999 in the U.S. and in 2001 in the U.K. (Pletal®) for the treatment of intermittent claudication symptoms. Despite its remarkable antiplatelet properties, CLZ is not generally considered an antithrombotic agent in Western countries, perhaps due to the bulk of its antithrombotic preclinical and clinical development being conducted in Japan. In this review, the unique properties of CLZ are reviewed with the focus on CLZ as a unique antiplatelet agent targeting platelets and VSMC, demonstrating synergy with endogenous mediators and showing lowered risk of bleeding risk compared to other antiplatelet drugs.

Keywords: cilostazol, pletaal, adenosine, antithrombotic, intermittent claudication, stroke, and restenosis


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