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Systematic (IUPAC) name
Clinical data
AHFS/ Monograph
MedlinePlus a601020
  • US: C (Risk not ruled out)
Routes of
IV only
Legal status
Legal status
  • ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 100% (as IV bolus, infusion)
Protein binding 70 to 80%
Metabolism Hepatic (12%)
Biological half-life 2.3 hours (mean, in CHF)
Excretion Urine (85% as unchanged drug) within 24 hours
CAS Number 78415-72-2 YesY
ATC code C01CE02 (WHO)
PubChem CID 4197
DrugBank DB00235 YesY
ChemSpider 4052 YesY
KEGG D00417 YesY
ChEBI CHEBI:50693 YesY
Chemical data
Formula C12H9N3O
Molar mass 211.219 g/mol
Physical data
Density 1.344 g/cm3
Melting point 315 °C (599 °F)
Boiling point 449 °C (840 °F)

Milrinone, commonly known and marketed under the brand name Primacor, is a medication used in patients who have heart failure. It is a phosphodiesterase 3 inhibitor that works to increase the heart's contractility and decrease pulmonary vascular resistance. Milrinone also works to vasodilate which helps alleviate increased pressures (afterload) on the heart, thus improving its pumping action. While it has been used in people with heart failure for many years, recent studies suggest that milrinone may exhibit some negative side effects that have caused some debate about its use clinically.[1][2]

Overall, milrinone supports ventricular functioning of the heart by decreasing the degradation of cAMP and thus increasing phosphorylation levels of many components in the heart that contribute to contractility and heart rate. Milrinone use following cardiac surgery has been under some debate because of the potential increase risk of postoperative atrial arrhythmias.[3] However, in the short term milrinone has been deemed beneficial to those experiencing heart failure and an effective therapy to maintain heart function following cardiac surgeries. There is no evidence of any long term beneficial effects on survival.[4]

Contractility in the heart[edit]

People experiencing some forms of heart failure have a significant decrease in the contractile ability of muscle cells in the heart (cardiomyocytes). This impaired contractility occurs through a number of mechanisms. Some of the main problems associated with decreased contractility in those with heart failure are issues arising from imbalances in the concentration of calcium. Calcium permits myosin and actin to interact which allows initiation of contraction within the cardiomyocytes. In those with heart failure there may be a decreased amount of calcium within the cardiomyocytes reducing the available calcium to initiate contraction. When contractility is decreased the amount of blood being pumped out of the heart into circulation is decreased as well. This reduction in cardiac output can cause many systemic implications such as fatigue, syncope and other issues associated with decreased blood flow to peripheral tissues.

Mechanism of action[edit]

Cyclic adenosine monophosphate (cAMP) causes increased activation of protein kinase A (PKA). PKA is an enzyme that phosphorylates many elements of the contractile machinery within the heart cell. In the short term this leads to an increased force of contraction. Phosphodiesterases are enzymes responsible for the breakdown of cAMP. Therefore, when phosphodiesterases lower the level of cAMP in the cell they also lower the active fraction of PKA within the cell and reduce the force of contraction.

Milrinone is a phosphodiesterase-3 inhibitor. This drug inhibits the action of phosphodiesterase-3 and thus prevents degradation of cAMP. With increased cAMP levels there is an increase in the activation of PKA. This PKA will phosphorylate many components of the cardiomyocyte such as calcium channels and components of the myofilaments. Phosphorylation of calcium channels permits an increase in calcium influx into the cell. This increase in calcium influx permits increased contractility. PKA also phosphorylates potassium channels promoting their action. Potassium channels are responsible for repolarization of the cardiomyocytes therefore increasing the rate at which cells can depolarize and generate contraction. PKA also phosphorylates components on myofilaments allowing actin and myosin to interact more easily and thus increasing contractility and the inotropic state of the heart. Milrinone allows stimulation of cardiac function independently of β-adrenergic receptors which appear to be down-regulated in those with heart failure.

Adverse effects[edit]

In recent years many studies have been performed showing that milrinone use may present potential adverse side effects in heart failure patients. Following cardiac surgery milrinone has been used as a therapy to maintain ventricular function of the heart. A study conducted by Fleming and colleagues has shown that milrinone use may be associated with increase atrial fibrillation following cardiac surgery. In another study by Smith and colleagues, milirinone appeared to generate a 3-fold increase in tachyarrhythmias following surgery for congenital heart disease. However, other studies suggest that milrinone is extremely beneficial in maintaining heart function in the short term following surgical procedures.[citation needed]


Milrinone Synthesis.png

Singh, B.; 1983, U.S. Patent 4,413,127.


  1. ^ Packer, M. Calcium channel blockers in chronic heart failure: The risks of ‘ physiologically rational ’ therapy [Editorial] . C irculation 8 2, 2254 – 2257.
  2. ^ Packer M, Carver J, Rodeheffer R, Ivanhoe R, DiBianco R, Zeldis S et al. Effect of Oral Milrinone on Mortality in Severe Chronic Heart Failure. The New England Journal of Medicine. 21 Nov 1991;325(21):1468-1475.
  3. ^ Fleming G, Murray K, Yu C, Byrne J, Greelish J, Petracek M et al. Milrinone Use Is Associated With Postoperative Atrial Fibrillation After Cardiac Surgery. The Journal of the American Heart Association. 29 Sept 2008;118:1619-1625.
  4. ^ British National Formulary. 66 ed. London: BMJ Group and Pharmaceutical Press; Sept 2013
  • Anonymous. Milrinone for Acute Exacerbations of CHF: Routine Use Not Recommended. Formulary Journal. May 2000;37(5): 227.
  • Sablotzki A, Starzmann W, Schebel R, Grond S and Czeslik E. Selective Pulmonary Vasodilation with Inhaled Aerosolized Milrinone in Heart Transplant Candidates. Canadian Journal of Anesthesia. 18 Apr 2005;52(10):1076-1083.
  • Smith A, Owen J, Borgman K, Fish F, and Kannankeril P. Relation of MIlrinone After Surgery for Congenital Heart Disease to Significant Postoperative Tachyarrhythmias. American Journal of Cardiology. 1 Dec 2011;108(11):1620-1624.
  • Yan C, Miller C and Abe, J. Regulation of Phosphodiesterase 3 and Inducible cAMP Early Repressor in the Heart. Circulation Research. 2007;100:589-501.
  • Yano M, Kohno M, Oskusa T, Mochizuki M, Yamada J, Kohno M et all. Effect of Milrinone On Left Ventricular Relaxation and Calcium Uptake Function of Cardiac Sarcoplasmic Reticulum. American Journal of Physiology. 9 May 2000;279(4):1898-1905.

External links[edit]