Minami N, Suzuki Y, Yamamoto M, Kihira H, Imai E, Wada H, Kimura Y, Ikeda Y, Shiku H, Nishikawa M
The 2nd Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan.
Life Sci. 1997;61(25):PL 383-9. doi: 10.1016/s0024-3205(97)00986-7.
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.
西洛他唑（6-[4-(1-环己基-1H-四氮唑-5-基)-丁氧基]-3,4-二氢-2(1H)-喹啉酮）可选择性抑制环磷酸鸟苷（cGMP）抑制的磷酸二酯酶（PDE3），并且是多种激动剂诱导的血小板聚集的强效抑制剂。在体外和体内研究了西洛他唑对剪切应力诱导的人血小板聚集（SIPA）的影响。西洛他唑在体外呈剂量依赖性地抑制SIPA。西洛他唑抑制SIPA的IC50值为15±2.6微摩尔（平均值±标准误，n = 5），这与抑制二磷酸腺苷（ADP）诱导的血小板聚集的IC50值（12.5±2.1微摩尔）非常相似。西洛他唑增强前列腺素E1（PGE1）对SIPA的抑制作用，并增强其增加环磷酸腺苷（cAMP）浓度的能力。对健康志愿者单次口服100毫克西洛他唑可显著抑制SIPA。本研究表明，西洛他唑是SIPA的有效抑制剂，这可能对动脉闭塞性疾病的预防和治疗具有重要意义。
