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Chemical Compound Review

Corotrop     6-methyl-2-oxo-5-pyridin-4- yl-1H-pyridine...

Synonyms: Primacor, Corotrope, Milrila, Milrinona, milrinone, ...
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Disease relevance of milrinone

  • We conclude that milrinone shows promise for the longterm treatment of congestive heart failure [1].
  • Furthermore, our data suggest that milrinone may aggravate ventricular arrhythmias [2].
  • Patients treated with milrinone had more hospitalizations (44 vs. 39 percent, P = 0.041), were withdrawn from double-blind therapy more frequently (12.7 vs. 8.7 percent, P = 0.041), and had serious adverse cardiovascular reactions, including hypotension (P = 0.006) and syncope (P = 0.002), more often than the patients given placebo [3].
  • We randomly assigned 1,088 patients with severe chronic heart failure (New York Heart Association class III or IV) and advanced left ventricular dysfunction to double-blind treatment with (40 mg of oral milrinone daily (561 patients) or placebo (527 patients) [3].
  • Chronic milrinone therapy after acute myocardial infarction improves cardiac hemodynamic indexes and attenuates progressive left ventricular dilation [4].

Psychiatry related information on milrinone


High impact information on milrinone

  • The left ventricular ejection fraction at rest was not significantly changed by milrinone (+0.2 percent; 95 percent confidence limits, -1.5 and 1.9), but it was increased by digoxin (+1.7 percent; P less than 0.01; 95 percent confidence limits, -0.03 and 3.4) and decreased by placebo (-2.0 percent; 95 percent confidence limits, -3.8 and -0.1) [2].
  • We conclude that milrinone significantly increased exercise tolerance and reduced the frequency of worsened heart failure [2].
  • In 20 patients with severe congestive heart failure, intravenous milrinone resulted in significant decreases in left ventricular end-diastolic pressure (from 27 +/- 2 to 18 +/- 2 mm Hg), pulmonary wedge pressure, right atrial pressure, and systemic vascular resistance, as well as a slight reduction in mean arterial pressure [1].
  • In this study, we show that NOS3 and mRNA and protein levels in cardiac myocytes are reduced both in vitro after treatment with cAMP elevating drugs, and in vivo after 3 d of treatment with milrinone, a type III cAMP phosphodiesterase inhibitor [6].
  • Because, in frog heart, the stimulatory effect of SIN-1 on ICa was found to be due to cGMP-induced inhibition of cGMP-inhibited phosphodiesterase (cGI-PDE), we compared the effects of SIN-1 and milrinone, a cGI-PDE selective inhibitor, on ICa in human [7].

Chemical compound and disease context of milrinone


Biological context of milrinone

  • Milrinone caused heart rate, stroke volume, and dP/dt to increase, and systemic vascular resistance to decrease in a concentration-related manner [8].
  • After intravenous administration of milrinone, peak negative dP/dt increased (+ 18%; p less than .01) and T decreased (-30%; p less than .01), while heart rate increased by only 8% (87 +/- 12 to 94 +/- 15 beats/min; p less than .01), left ventricular systolic pressure did not change, and mean aortic pressure fell by 11% (p less than .01) [13].
  • This forearm vasodilatation occurred without change in systemic hemodynamics or therapeutic milrinone plasma concentrations in the pulmonary artery [14].
  • The pharmacokinetics of milrinone were studied in sequential ascending doses in New York Heart Association Class III and IV patients receiving oral and intravenous medication [15].
  • Milrinone (0.2 to 20 micrograms/ml) caused no major changes in the action potential characteristics, refractoriness, or conduction velocity in fibers exposed to normal Tyrode's solution, but markedly improved conduction and abbreviated or eliminated postrepolarization refractoriness in the ischemic gap preparations [16].

Anatomical context of milrinone


Associations of milrinone with other chemical compounds

  • To clarify further the role of a positive inotropic action, the relative effects of milrinone and nitroprusside on left ventricular stroke work and dP/dt were compared in each patient at doses matched to cause equivalent reductions in mean arterial pressure or systemic vascular resistance, indices of left ventricular afterload [8].
  • Both the heart rate-blood pressure product (9624 +/- 2272 to 9380 +/- 2428 mm Hg-beats/min; p = NS) and regional left ventricular myocardial oxygen consumption (7.6 +/- 2.9 to 8.1 +/- 3.1 ml O2/min; p = NS) were unchanged after milrinone, resulting in a 45% increase in calculated left ventricular external efficiency (p = .004) [21].
  • Femoral vein oxygen content was increased by milrinone from 7.9 +/- 2.6 to 9.8 +/- 3.0 ml/100 ml (p less than .05) and was not changed by captopril [22].
  • X-ray crystallographic analysis of milrinone and amrinone revealed structural homologies between the phenolic ring of thyroxine and the substituted ring of milrinone, whereas amrinone did not share these homologies [23].
  • Pimobendan, in a dose-dependent manner, increased active tension developed by chemically-skinned dog heart muscle fibers at submaximally activating concentrations of Ca2+, whereas milrinone did not [24].

Gene context of milrinone


Analytical, diagnostic and therapeutic context of milrinone

  • In 10 patients receiving long-term oral milrinone (greater than or equal to 6 months) radionuclide ventriculography showed continued responsiveness, with a 27 per cent increase in left ventricular ejection fraction after 7.5 mg of the drug [1].
  • Cardiotonic agent milrinone stimulates resorption in rodent bone organ culture [17].
  • In nine patients radionuclide ventriculographic studies were performed during left heart catheterization, allowing calculation of left ventricular peak filling rate, volumes, and the diastolic pressure-volume relationship before and after milrinone [13].
  • Dobutamine and milrinone were administered intravenously according a graded titration schedule up to maximum doses (14 micrograms/kg/min and 75 micrograms/kg, respectively) or until increased ventricular ectopy or a reduction in left ventricular end-diastolic pressure to 10 mm Hg or less occurred [29].
  • In this study microelectrode techniques were used to assess the electrophysiologic effects of milrinone in canine false tendons homogeneously superfused with either normal or high-K Tyrode's solution and in Purkinje fibers mounted in a three-compartment chamber in which the central segment was depressed with an "ischemic" solution [16].


  1. Evaluation of a new bipyridine inotropic agent--milrinone--in patients with severe congestive heart failure. Baim, D.S., McDowell, A.V., Cherniles, J., Monrad, E.S., Parker, J.A., Edelson, J., Braunwald, E., Grossman, W. N. Engl. J. Med. (1983) [Pubmed]
  2. A comparison of oral milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure. DiBianco, R., Shabetai, R., Kostuk, W., Moran, J., Schlant, R.C., Wright, R. N. Engl. J. Med. (1989) [Pubmed]
  3. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. Packer, M., Carver, J.R., Rodeheffer, R.J., Ivanhoe, R.J., DiBianco, R., Zeldis, S.M., Hendrix, G.H., Bommer, W.J., Elkayam, U., Kukin, M.L. N. Engl. J. Med. (1991) [Pubmed]
  4. Effects of milrinone on left ventricular remodeling after acute myocardial infarction. Jain, P., Brown, E.J., Langenback, E.G., Raeder, E., Lillis, O., Halpern, J., Mannisi, J.A. Circulation (1991) [Pubmed]
  5. The effect of the specific phosphodiesterase (PDE) inhibitors on human and rabbit cavernous tissue in vitro and in vivo. Stief, C.G., Uckert, S., Becker, A.J., Truss, M.C., Jonas, U. J. Urol. (1998) [Pubmed]
  6. Nitric oxide synthase (NOS3) and contractile responsiveness to adrenergic and cholinergic agonists in the heart. Regulation of NOS3 transcription in vitro and in vivo by cyclic adenosine monophosphate in rat cardiac myocytes. Belhassen, L., Kelly, R.A., Smith, T.W., Balligand, J.L. J. Clin. Invest. (1996) [Pubmed]
  7. Nitric oxide regulates the calcium current in isolated human atrial myocytes. Kirstein, M., Rivet-Bastide, M., Hatem, S., Bénardeau, A., Mercadier, J.J., Fischmeister, R. J. Clin. Invest. (1995) [Pubmed]
  8. Positive inotropic and vasodilator actions of milrinone in patients with severe congestive heart failure. Dose-response relationships and comparison to nitroprusside. Jaski, B.E., Fifer, M.A., Wright, R.F., Braunwald, E., Colucci, W.S. J. Clin. Invest. (1985) [Pubmed]
  9. Systemic and coronary effects of intravenous milrinone and dobutamine in congestive heart failure. Grose, R., Strain, J., Greenberg, M., LeJemtel, T.H. J. Am. Coll. Cardiol. (1986) [Pubmed]
  10. Identification of interaction sites of cyclic nucleotide phosphodiesterase type 3A with milrinone and cilostazol using molecular modeling and site-directed mutagenesis. Zhang, W., Ke, H., Colman, R.W. Mol. Pharmacol. (2002) [Pubmed]
  11. Regional blood flow and neurohormonal responses to milrinone in congestive heart failure. Cody, R.J., Kubo, S.H., Covit, A.B., Müller, F.B., Rutman, H., Leonard, D., Laragh, J.H., Feldschuh, J., Preibisz, J. Clin. Pharmacol. Ther. (1986) [Pubmed]
  12. AQP3, p-AQP2, and AQP2 expression is reduced in polyuric rats with hypercalcemia: prevention by cAMP-PDE inhibitors. Wang, W., Li, C., Kwon, T.H., Knepper, M.A., Frøkiaer, J., Nielsen, S. Am. J. Physiol. Renal Physiol. (2002) [Pubmed]
  13. Improvement in indexes of diastolic performance in patients with congestive heart failure treated with milrinone. Monrad, E.S., McKay, R.G., Baim, D.S., Colucci, W.S., Fifer, M.A., Heller, G.V., Royal, H.D., Grossman, W. Circulation (1984) [Pubmed]
  14. Identification of the direct vasodilator effect of milrinone with an isolated limb preparation in patients with chronic congestive heart failure. Cody, R.J., Müller, F.B., Kubo, S.H., Rutman, H., Leonard, D. Circulation (1986) [Pubmed]
  15. Pharmacokinetics of the bipyridines amrinone and milrinone. Edelson, J., Stroshane, R., Benziger, D.P., Cody, R., Benotti, J., Hood, W.B., Chatterjee, K., Luczkowec, C., Krebs, C., Schwartz, R. Circulation (1986) [Pubmed]
  16. The effects of milrinone on conduction, reflection, and automaticity in canine Purkinje fibers. Davidenko, J.M., Antzelevitch, C. Circulation (1984) [Pubmed]
  17. Cardiotonic agent milrinone stimulates resorption in rodent bone organ culture. Krieger, N.S., Stappenbeck, T.S., Stern, P.H. J. Clin. Invest. (1987) [Pubmed]
  18. The inotropic effects of amrinone and milrinone on neonatal and young canine cardiac muscle. Binah, O., Sodowick, B., Vulliemoz, Y., Danilo, P., Rosen, M. Circulation (1986) [Pubmed]
  19. In vivo studies of myocardial beta-adrenergic receptor pharmacology in patients with congestive heart failure. Colucci, W.S. Circulation (1990) [Pubmed]
  20. Pharmacology of the bipyridines: amrinone and milrinone. Alousi, A.A., Johnson, D.C. Circulation (1986) [Pubmed]
  21. Effects of milrinone on coronary hemodynamics and myocardial energetics in patients with congestive heart failure. Monrad, E.S., Baim, D.S., Smith, H.S., Lanoue, A., Brauwald, E., Grossman, W. Circulation (1985) [Pubmed]
  22. Systemic and regional hemodynamic effects of captopril and milrinone administered alone and concomitantly in patients with heart failure. LeJemtel, T.H., Maskin, C.S., Mancini, D., Sinoway, L., Feld, H., Chadwick, B. Circulation (1985) [Pubmed]
  23. Milrinone and thyroid hormone stimulate myocardial membrane Ca2+-ATPase activity and share structural homologies. Mylotte, K.M., Cody, V., Davis, P.J., Davis, F.B., Blas, S.D., Schoenl, M. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  24. Sensitization of dog and guinea pig heart myofilaments to Ca2+ activation and the inotropic effect of pimobendan: comparison with milrinone. Fujino, K., Sperelakis, N., Solaro, R.J. Circ. Res. (1988) [Pubmed]
  25. Gene expression of the phosphodiesterases 3A and 5A in human corpus cavernosum penis. Küthe, A., Mägert, H., Uckert, S., Forssmann, W.G., Stief, C.G., Jonas, U. Eur. Urol. (2000) [Pubmed]
  26. Isolation and characterization of a previously undetected human cAMP phosphodiesterase by complementation of cAMP phosphodiesterase-deficient Saccharomyces cerevisiae. Michaeli, T., Bloom, T.J., Martins, T., Loughney, K., Ferguson, K., Riggs, M., Rodgers, L., Beavo, J.A., Wigler, M. J. Biol. Chem. (1993) [Pubmed]
  27. Pharmacological modulation of myocardial tumor necrosis factor alpha production by phosphodiesterase inhibitors. Bergman, M.R., Holycross, B.J. J. Pharmacol. Exp. Ther. (1996) [Pubmed]
  28. Modulation of TNF and GM-CSF release from dispersed human nasal polyp cells and human whole blood by inhibitors of different PDE isoenzymes and glucocorticoids. Marx, D., Tassabehji, M., Heer, S., Hüttenbrink, K.B., Szelenyi, I. Pulmonary pharmacology & therapeutics. (2002) [Pubmed]
  29. Milrinone and dobutamine in severe heart failure: differing hemodynamic effects and individual patient responsiveness. Colucci, W.S., Wright, R.F., Jaski, B.E., Fifer, M.A., Braunwald, E. Circulation (1986) [Pubmed]
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