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Thromb Haemost 1999; 82(02): 435-438
DOI: 10.1055/s-0037-1615863
Research Article
Schattauer GmbH

Antiplatelet Therapy Using Cilostazol, a Specific PDE3 Inhibitor

Yasuo Ikeda
1   Division of Hematology, Department of Internal Medicine, Keio University, Tokyo, JAPAN
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Publication Date:
09 December 2017 (online)

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Introduction

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.
    PubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 3 Takahashi S, Oida K, Fujiwara R, Maeda H, Hayashi S, Takai H, Tamai T, Nakai T, Miyabo S. Effect of cilostazol, a cyclic AMP phosphodiesterase inhibitor, on the proliferation of rat aortic smooth muscle cells in culture. J Cardiovasc Pharmacol 1992; 20: 900-906.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 5 Beavo JA, Conti M, Heaslip RJ. Multiple cyclic nucleotide phosphodiesterases. Mol Pharmacol 1994; 46: 399-405.
    PubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    PubMedGoogle Scholar
  • 10 Igawa T, Tani T, Chijiwa T, Shiragiku T, Shimizu S, Kawamura K, Kato S, Unomi F, Kimura Y. Potentiation of anti-platelet aggregating activity of cilostazol with vascular endothelial cells. Thromb Res 1990; 57: 617-623.
    CrossrefPubMedGoogle Scholar
  • 11 Watanabe K, Nakase H, Kimura Y. Effect of cilostazol on experimental cerebral infarction in rabbits. Arzneimittelforschung 1986; 36: 1022-1024.
    PubMedGoogle Scholar
  • 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.
    PubMedGoogle Scholar
  • 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.
    PubMedGoogle Scholar
  • 14 Saitoh S, Saito T, Otake A, Owada T, Mitsugi M, Hashitoto H, Maruyama Y. Cilostazol, a novel cyclic AMP phosphodiesterase inhibitor, prevents reocclusion after coronary arterial thrombolysis with recombinant tissue-type plasminogen activator. Arterioscler Thromb 1993; 13: 563-570.
    CrossrefPubMedGoogle Scholar
  • 15 Kawamura K, Watanabe K, Kimura Y. Effect of cilostazol, a new antithrombotic drug, on cerebral circulation. Arzneimittelforschung 1985; 35: 1149-1154.
    PubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 21 Elam MB, Heckman J, Crouse JR, Hunninghake DB, Herd JA, Davidson M, Gordon IL, Bortey EB, Forbes WP. Effect of the novel antiplatelet agent cilostazol on plasma lipoproteins in patients with intermittent claudication. Arterioscler Thromb Vasc Biol 1998; 18: 1942-1947.
    CrossrefPubMedGoogle Scholar
  • 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.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 27 Dawson DL, Cutler BS, Meissner MH, Strandness DE. Cilostazol has beneficial effects in treatment of intermittent claudication. Circulation 1998; 98: 678-686.
    CrossrefPubMedGoogle Scholar
  • 28 Yasuda K, Sakuma M, Tanabe T. Hemodynamic effect of cilostazol on increasing peripheral blood flow in arteriosclerosis obliterans. Arzneimittelforschung 1985; 35: 1198-1200.
    PubMedGoogle Scholar
  • 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.
    PubMedGoogle Scholar