生物活性

• 描述Cyclic nucleotide phosphodiesterases (PDEs) from the human heart were separated into three isoforms, FI, FII and FIII. Milrinone has been proved to be a potent and selective inhibitor of human cardiac FIII PDE, a "low Km" enzyme for cyclic AMP (cAMP-PDE). The IC₅₀ value for the inhibition of FIII PDE was 0.42 μM, while those of FI and FII PDEs, "high Km" enzymes, were 38 and 19 μM, respectively^[3]. The concentration of milrinone that produced 50% relaxation of tracheal spirals constricted by carbachol was 3.6 × 10^-5 M; The IC₅₀ for milrinone for lung parenchymal strips contracted by histamine was 3.2 × 10^-5 M; Milrinone relaxed pulmonary artery rings constricted by norepinephrine with an IC₅₀ of 3.8 × 10^-6 M^[4]. Milrinone caused a concentration-dependent increase in the cAMP level in rabbit and human platelets with similar potency. Furthermore, milrinone inhibited human platelet aggregation with an IC₅₀ of 2 μM. It was a very potent cardiotonic agent, which concentration-dependently increased left ventricular developed pressure (LVDP) and contractility as well as cAMP in rabbit coronary smooth muscle cells^[5]. In rabbit heart, partial inhibition of PDE4 by milrinone contributed to greater increases in cardiomyocyte cAMP and calcium levels^[6]. In mongrel dogs underwent pulmonary artery catheterization, Milrinone led to significant increases in right ventricular function as well as significant improvements in pulmonary vascular resistance, pulmonary blood flow, and left ventricular filling^[7].
• 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
  NCT02606253	Heart Failure	Phase 4	Active, not recruiting	October 31, 2018	United States, Tennessee ... more >> Vanderbilt University Medical Center Nashville, Tennessee, United States, 37204 Collapse <<
  NCT02884011	-	-	Completed	-	United States, Illinois ... more >> Rush Univeristy Medical Center Chicago, Illinois, United States, 60612 Collapse <<
  NCT02261506	Bacteremia	Not Applicable	Completed	-	Canada, Alberta ... more >> Foothills Hospital Calgary, Alberta, Canada University of Alberta Hospital Edmonton, Alberta, Canada Canada, British Columbia Royal Columbian Hospital Vancouver, British Columbia, Canada St. Paul's Hospital Vancouver, British Columbia, Canada Canada, Manitoba St. Boniface Hospital Winnipeg, Manitoba, Canada Canada, Nova Scotia Queen Elizabeth II Hospital Halifax, Nova Scotia, Canada Canada, Ontario Kingston General Hospital Kingston, Ontario, Canada London Health Sciences Centre London, Ontario, Canada The Ottawa Hospital Ottawa, Ontario, Canada Sunnybrook Health Sciences Centre Toronto, Ontario, Canada, M4N3M5 Mount Sinai Hospital Toronto, Ontario, Canada St. Michael's Hospital Toronto, Ontario, Canada Toronto Western Hospital Toronto, Ontario, Canada Canada, Quebec CHUM Montreal, Quebec, Canada Université de Sherbrooke Sherbrooke, Quebec, Canada Canada Centre hospitalier affilié universitaire de Québec Quebec, Canada CSSS de Trois-Rivières Quebec, Canada Collapse <<

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• 参考文献

• [1] 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.

  [2] Shipley JB, Tolman D, et al. Milrinone: basic and clinical pharmacology and acute and chronic management. Am J Med Sci. 1996 Jun;311(6):286-91.

  [3] Ito M, Tanaka T, Saitoh M, Masuoka H, Nakano T, Hidaka H. Selective inhibition of cyclic AMP phosphodiesterase from various human tissues by milrinone, a potent cardiac bipyridine. Biochem Pharmacol. 1988 May 15;37(10):2041-4. doi: 10.1016/0006-2952(88)90554-0. PMID: 2837222.

  [4] Rossing TH, Drazen JM. Effects of milrinone on contractile responses of guinea pig trachea, lung parenchyma and pulmonary artery. J Pharmacol Exp Ther. 1986 Sep;238(3):874-9. PMID: 3746666.

  [5] Cone J, Wang S, Tandon N, Fong M, Sun B, Sakurai K, Yoshitake M, Kambayashi J, Liu Y. 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. doi: 10.1097/00005344-199910000-00004. PMID: 10511123.

  [6] Shakur Y, Fong M, Hensley J, Cone J, Movsesian MA, Kambayashi J, Yoshitake M, Liu Y. Comparison of the effects of cilostazol and milrinone on cAMP-PDE activity, intracellular cAMP and calcium in the heart. Cardiovasc Drugs Ther. 2002 Sep;16(5):417-27. doi: 10.1023/a:1022186402442. PMID: 12652111.

  [7] Chen EP, Bittner HB, Davis RD Jr, Van Trigt P 3rd. Milrinone improves pulmonary hemodynamics and right ventricular function in chronic pulmonary hypertension. Ann Thorac Surg. 1997 Mar;63(3):814-21. doi: 10.1016/s0003-4975(97)00011-8. PMID: 9066407.

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