| Size | Price | Stock | Qty |
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| 250mg |
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| 500mg |
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| 1g |
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| 10g |
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Purity: ≥98%
Milrinone (formerly known as Win-47203; Win 47203; trade name Primacor) is a potent and selective phosphodiesterase 3 (PDE3) inhibitor that is used as a pulmonary vasodilator to increase the heart's contractility. Milrinone has shown the effect of concentration-dependent inhibition of PDE3 on the photolabelling with a IC50 value of 56±12nM. In addition, Milrinone has been reported to increase the accumulation of [3H] cAMP with a EC50 value of 5329±970nM in platelets.
| ln Vitro |
PKA activity in hypoxic myocytes is raised to normoxic levels by 1 µM milrinone. By reinstating PKA-mediated regulatory TP receptor phosphorylation, milrinone (50 nM) restores TP receptor sensitivity in hypoxic myocytes[1]. Milrinone attenuates maximal tension generation and NE sensitivity by substantially reducing NE-induced vasoconstriction. Milrinone-induced attenuation of NE responses is not prevented by voltage-gated or ATP-sensitive K+ channel inhibition[4].
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| ln Vivo |
In rats with congestive heart failure (CHF), milrinone (1 μg/kg/min, iv) dramatically lowers PAP, PVR (−18.96 ± 1.7%), and LAP (−26.03 ± 2.3%). Inhaling 1 mg/mL of milrinone reduces PAP almost to its near-maximum without having a substantial impact on AP. A bigger group of CHF rats also experience a comparable decrease in pulmonary artery pressure. In both groups, inhaling milrinone selectively raises the amounts of cAMP but not cGMP in the plasma. Milrinone inhalations repeated over time even lower the ratio of lung wet to dry weight[2]. At a mid-range LV volume (0.08 mL/g myocardium), milrinone (49.5 μg) considerably raises the systolic pressure-volume area (PVA(0.08)) and end-systolic pressure (ESP(0.08)). It also moves the ESPVR upward. Additionally, mildrinone modestly reduces Ea and LV ESP(ESV)[3].
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| Animal Protocol |
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
When administered as an IV bolus dose of 10-100 μg/kg, milrinone induces hemodynamic effects within 60 seconds reaching a peak effect by 2-5 minutes. The plasma AUC is significantly dose-dependent. Milrinone is primarily excreted in the urine, with 60% of a dose recovered after two hours and 90% within eight hours. Approximately 83% of milrinone recovered in urine is unchanged while 12% is present as the main O-glucuronide metabolite. Milrinone administered intravenously to congestive heart failure patients had a volume of distribution of 0.38 L/kg (injections between 12.5-125 μg/kg) and 0.45 L/kg (infusions between 0.2-0.7 μg/kg/min. Milrinone administered intravenously to congestive heart failure patients had a clearance of 0.13 L/kg/hr (injections between 12.5-125 μg/kg) and 0.14 L/kg/hr (infusions between 0.2-0.7 μg/kg/min. Metabolism / Metabolites Animal studies suggest that two oxidative pathways are involved in milrinone metabolism, albeit only involving a small proportion of the administered dose. The major metabolite is the O-glucuronide metabolite. Biological Half-Life Milrinone administered intravenously to congestive heart failure patients had a mean terminal elimination half-life of 2.3 hours (injections between 12.5-125 μg/kg) and 2.4 hours (infusions between 0.2-0.7 μg/kg/min. |
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| Toxicity/Toxicokinetics |
Protein Binding
Milrinone is approximately 70% bound to human plasma proteins. |
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| References |
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| Additional Infomation |
Pharmacodynamics
Milrinone is a bipyridine derivative with positive inotropic and lusitropic effects that also results in peripheral vasodilation with minimal chronotropic effects over a therapeutic range of 100 to 300 ng/mL. As such, milrinone is used in decompensated congestive heart failure. Studies have demonstrated that milrinone exhibits sigmoidal effects, such that increasing milrinone plasma concentrations beyond a certain level results in no further hemodynamic changes. Despite milrinone's benefits, both intravenous and oral use has been associated with increased frequency of ventricular arrhythmias, and long-term oral use has been associated with an increased risk of sudden death; in general, there are no data to support the safety or efficacy of milrinone use beyond 48 hours and patients should be monitored closely for cardiac dysfunction. Also, as milrinone is primarily excreted renally, dose adjustments may be required in patients with impaired renal function. |
| Molecular Formula |
C12H9N3O
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| Molecular Weight |
211.22
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| Exact Mass |
211.074
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| CAS # |
78415-72-2
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| Related CAS # |
Milrinone lactate;100286-97-3;Milrinone-d3;2749393-50-6
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| PubChem CID |
4197
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
448.7±45.0 °C at 760 mmHg
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| Melting Point |
>3000C
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| Flash Point |
225.2±28.7 °C
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| Vapour Pressure |
0.0±1.1 mmHg at 25°C
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| Index of Refraction |
1.622
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| LogP |
0.41
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
16
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| Complexity |
419
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
PZRHRDRVRGEVNW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H9N3O/c1-8-11(9-2-4-14-5-3-9)6-10(7-13)12(16)15-8/h2-6H,1H3,(H,15,16)
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| Chemical Name |
6-methyl-2-oxo-5-pyridin-4-yl-1H-pyridine-3-carbonitrile
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (13.02 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.75 mg/mL (13.02 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.7344 mL | 23.6720 mL | 47.3440 mL | |
| 5 mM | 0.9469 mL | 4.7344 mL | 9.4688 mL | |
| 10 mM | 0.4734 mL | 2.3672 mL | 4.7344 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05122884 | Recruiting | Drug: Milrinone | Septic Shock Cardiac Output |
Mahidol University | December 1, 2021 | Phase 2 |
| NCT06077721 | Recruiting | Drug: Milrinone | Ischemic Heart Disease Valvular Heart Disease |
Konkuk University Medical Center | November 3, 2023 | |
| NCT04484675 | Recruiting | Drug: Milrinone inhalation Drug: Milrinone infusion |
Pulmonary Hypertension Due to Left Heart Disease |
Zagazig University | January 20, 2022 | Phase 4 |
| NCT04362527 | Recruiting | Drug: Milrinone 1 Mg/mL Solution for Injection |
Vasospasm | University Hospital, Angers | August 10, 2020 | Phase 3 |
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