Cilostazol, 6-[ 4-( l-cyclohexy l-IH-tetrazol-5yl ) butoxy ]-3, 4-dihydro-2 (1H)-quinolinone, is an antiplatelet/ antithrombotic agent that has been used since 1988 in several countries, including Japan, for treatment of chronic peripheral arterial occlusion. Cilostazol was also approved by the United States Food and Drug Administration (FDA) in 1999 for the treatment of intermittent claudication. Cilostazol not only inhibits platelet activation but also increases vasodilation.1,2 In addition, it has been also shown to inhibit vascular smooth muscle cell proliferation.3 These properties of cilostazol may also improve peripheral blood flow. The mechanism of these effects is mediated through elevated cyclic adenosine monophosphate (AMP), brought about by inhibition of cyclic nucleotide phosphodiesterase (PDE3) activity.4 In this chapter, the pharmacological properties, as well as the clinical efficacy of cilostazol, are briefly discussed.
References
1
Kimura Y,
Tani T,
Kanbe T,
Watanabe K.
Effect of cilostazol on platelet aggregation and experimental thrombosis. Arzneimittelforschung 1985; 35: 1144-1149.
2
Tanaka T,
Ishikawa T,
Hagiwara M,
Onoda K,
Itoh H,
Hidaka H.
Effects of cilostazol, a selective cAMP phosphodiesterase inhibitor on the contraction of vascular smooth muscle. Pharmacology 1988; 36: 313-320.
4
Umekawa H,
Tanaka T,
Kimura Y,
Hidaka H.
Purification of cyclic adenosine monophosphate phosphodiesterase from human platelets using new-inhibitor Sepharose chromatography. Biochem Pharmacol 1984; 33: 3339-3344.
6
Soderling SH,
Bayuga SJ,
Beavo JA.
Identification and characterization of a novel family of cyclic nucleotide phosphodiesterases. J Biol Chem 1998; 273: 15553-15558.
7
Sudo T,
Inoue Y,
Tochizawa S,
Toga K,
Tachibana K,
Kimura Y,
Hidaka H.
Pharmacological characterization of a novel selective and potent cyclic nucleotide phosphodiesterase 3 inhibitor, OPC-33540. Jpn J Pharmacol 1998; 76: 213P.
8
Minami N,
Suzuki Y,
Yamamoto M,
Kihira H,
Imai E,
Wada H,
Kimura Y,
Ikeda Y,
Shiku H,
Nishikawa M.
Inhibition of shear stress-induced platelet aggregation by cilostazol, a specific inhibitor of cGMP-inhibited phosphodicsterase, in vitro and ex vivo. Life Sci 1997; 61 PL 383-389.
9
Ikeda Y,
Kikuchi M,
Murakami H,
Satoh K,
Ando Y.
Comparison of the inhibitory effects of cilostazol, acetylsalicylic acid and ticlopidine on platelet functions ex vivo: randomized, double-blind cross-over study. Arzneimittelforschung 1987; 37: 563-566.
12
Kawamura K,
Fujita S,
Tani T,
Kimura Y.
Effect of cilostazol, a new antithrombotic drug, on an experimental model of peripheral circulation insufficiency. Arzneimittelforschung 1985; a; 35: 1154-1156.
13
Yasuda K,
Tanabe T,
Hashimoto M,
Suzuki S,
Shimizu T,
Hosokawa Y.
Effect of cilostazol, a new antithrombotic drug, on small arterial replacement. Thromb Haemost 1985; 35: 1189-1192.
15
Kawamura K,
Watanabe K,
Kimura Y.
Effect of cilostazol, a new antithrombotic drug, on cerebral circulation. Arzneimittelforschung 1985; 35: 1149-1154.
16
Shiraishi Y,
Kanmura Y,
Ito T.
Effect of cilostazol, a phosphodiesterase type III inhibitor, on histamine-induced increase in [Ca2+]i and force in middle cerebral artery of the rabbit. Br J Pharmacol 1998; 123: 869-878.
17
Indolfi C,
Avvedimento EV,
Lorenzo ED,
Esposito G,
Rapacciuolo A,
Giuliano P,
Grieco D,
Cavuto L,
Stingone AM,
Ciullo I,
Condorelli G,
Chiariello M.
Activation of cAMP-PKA signaling in vivo inhibits smooth muscle cell proliferation induced by vascular injury. Nat Med 1997; 3: 775-779.
18
Kondo K,
Umemura K,
Miyaji M,
Nakashima M.
Milrinone, a phosphodiesterase inhibitor, suppresses intimal thickening after photochemically induced endothelial injury in the mouse femoral artery. Atherosclerosis 1999; 142: 133-138.
19
Sekiya M,
Funada J,
Watanabe K,
Miyagawa M,
Akutsu H.
Effects of probucol and cilostazol alone and in combination on frequency of poststenting restenosis. Am J Cardiol 1998; 82: 144-147.
20
Tsuchikane E,
Katoh O,
Sumitsuji S,
Fukuhara A,
Funamoto M,
Otsuji S,
Tateyama H,
Awata N,
Kobayashi T.
Impact of cilostazol on intimal proliferation after directional coronary atherectomy. Am Heart J 1998; 135: 495-502.
22
Nomura S,
Shouzu A,
Omoto S,
Hayakawa T,
Kagawa H,
Nishikawa M,
Inada M,
Fujimura Y,
Ikeda Y,
Fukuhara S.
Effect of cilostazol on soluble adhesion molecules and platelet-derived microparticles in patients with diabetes. Thromb Haemost 1998; 80: 388-392.
23
Yamasaki M,
Hara K,
Ikari Y,
Kobayashi N.
Effects of cilostazol on late lumen loss after Palmaz-Schatz stent implantation. Cathet Cardiovasc Diagn 1998; 44: 387-391.
24
Ochiai M,
Isshiki t,
Takeshita S,
Eto K.
Use of cilostazol, a novel antiplatelet agent, in a post-Palmaz-Schatz stenting regimen. Am J Cardiol 1997; 79: 1471-1474.
25
Schomig A,
Neumann FJ,
Kastrati A,
Schuhlen H.
A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stent. N Engl J Med 1996; 334: 1084-1089.
26
Take S,
Matsutani M,
Ueda H,
Hamaguchi H.
Effect of cilostazol in preventing restenosis after percutaneous transluminal coronary angioplasty. Am J Cardiol 1997; 79: 1097-1099.
28
Yasuda K,
Sakuma M,
Tanabe T.
Hemodynamic effect of cilostazol on increasing peripheral blood flow in arteriosclerosis obliterans. Arzneimittelforschung 1985; 35: 1198-1200.
29
Uchikawa T,
Murakami T,
Furukawa H.
Effects of the antiplatelet agent, cilostazol on peripheral vascular disease in patients with diabetes mellitus. Arzneimittelforschung 1992; 42: 322-324.
