生物活性

• 描述Type 3 cyclic nucleotide phosphodiesterase (PDE-3) isoforms exhibit a high affinity ("low K(m)") for cAMP and are specifically inhibited by cGMP and a number of pharmacological agents. The PDE-3 family consists of at least two isozymes, PDE-3A (cardiac type) and PDE-3B (adipocyte type), with distinct tissue-specific distributions^[3]. Cilostazol is a 2-oxo-quinoline derivative with antithrombotic, vasodilator, antimitogenic and cardiotonic properties. The compound is a potent inhibitor of phosphodiesterase (PDE) 3A, the isoform of PDE 3 in the cardiovascular system (IC₅₀: 0.2 μM). There is no relevant effect by cilostazol on PDE 1, 2 and 4 at comparable concentrations, and only a minor effect on PDE 5 (IC₅₀: 5 ± 8 mM). In addition, there was inhibition of adenosine uptake, eventually resulting in changes in cAMP levels^[4]. In vitro, cilostazol inhibited adenosine uptake into cardiac myocytes, coronary artery smooth muscle cells and endothelial cells, with a median effective concentration of 10 μM, which might result from stimulation of adenosine A1 receptors and might counteract the increase of cAMP via PDE-inhibition^[4]. Cilostazol inhibits platelet aggregation and has considerable antithrombotic effects in vivo. The compound relaxed vascular smooth muscle and inhibited mitogenesis and migration of vascular smooth muscle cells and decreaseed levels of serum triglycerides and caused some increase in HDL-cholesterol levels^[4]. In the rat carotid injury model, single local application of cilostazol resulted in a marked inhibition of intima proliferation. Interestingly, the tissue concentration of cilostazol in the carotid artery and muscle around the carotid artery was considerably higher than in plasma, which was probably related to its highly lipophilic nature. There was also suppression of neointimal formation in dog grafted veins, which appeared to be related to inhibition of angiotensin II forming enzymes^[4].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01515228	Coronary Artery Disease	Phase 4	Completed	-	Korea, Republic of ... more >> Soon Chun Hyang University Hospital Cheonan Cheonan, Korea, Republic of Daegu Catholic University Medical Center Daegu, Korea, Republic of Keimyung University Dongsan Medical Center Daegu, Korea, Republic of Chungnam National University Hospital Daejeon, Korea, Republic of The Catholic University of Korea, Daejeon ST. Mary's Hospital Daejeon, Korea, Republic of Gangneung Asan Hospital Gangneung, Korea, Republic of Inje University Pusan Paik Hospital Pusan, Korea, Republic of Asan Medical Center Seoul, Korea, Republic of Ulsan University Hospital Ulsan, Korea, Republic of Collapse <<
  NCT00300339	Intermittent Claudication	Phase 2	Completed	-	United States, New Jersey ... more >> Sanofi-Aventis Administrative Office Bridgewater, New Jersey, United States, 08807 Belgium Sanofi-Aventis Administrative Office Diegem, Belgium Canada Sanofi-Aventis Administrative Office Laval, Canada Czech Republic Sanofi-Aventis Administrative Office Praha, Czech Republic Germany Sanofi-Aventis Administrative Office Berlin, Germany Mexico Sanofi-Aventis Administrative Office Mexico, Mexico Russian Federation Sanofi-Aventis Administrative Office Moscow, Russian Federation Sweden Sanofi-Aventis Administrative Office Bromma, Sweden Ukraine Sanofi-Aventis Administrative Office Kiev, Ukraine Collapse <<
  NCT01955200	Coronary Artery Disease	Phase 4	Unknown	December 2016	China, Jiangsu ... more >> First Affiliated Hospital of Nanjing Medical University Recruiting Nanjing, Jiangsu, China, 210029 Contact: Fuming Zhang, M.D.    +86-25-83718836 ext 6360    jsphkj@163.com    Contact: Yi Chai, M.D.    +86-25-83718836 ext 6360    jsphkj@163.com    Sub-Investigator: Dingguo Zhang, Ph.D Collapse <<

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• 参考文献

• [1] Liu Y, Shakur Y, et al. Cilostazol (pletal): a dual inhibitor of cyclic nucleotide phosphodiesterase type 3 and adenosine uptake. Cardiovasc Drug Rev. 2001 Winter;19(4):369-86.

  [2] Cone J, Wang S, et al. Comparison of the effects of cilostazol and milrinone on intracellular cAMP levels and cellular function in platelets and cardiac cells. J Cardiovasc Pharmacol. 1999 Oct;34(4):497-504.

  [3] Nagaoka T, Shirakawa T, Kasuya J, Balon TW, Manganiello VC, Fujita-Yamaguchi Y. Cyclic nucleotide PDE-3. Quantitation of PDE-3A and -3B mRNAs in rat tissues by RNase protection assay. Cell Biochem Biophys. 1998;29(1-2):49-66. doi: 10.1007/BF02737828. PMID: 9631238.

  [4] Schrör K. The pharmacology of cilostazol. Diabetes Obes Metab. 2002 Mar;4 Suppl 2:S14-9. doi: 10.1046/j.1463-1326.2002.0040s2s14.x. PMID: 12180353.