Milrinone
[CAS# 78415-72-2]

Identification

• Classification: API >> Circulatory system medication >> Anti-congestive heart failure medicine
• Name: Milrinone
• Synonyms: 1,6-Dihydro-2-methyl-6-oxo-(3,4'-bipyridine)-5-carbonitrile
• Molecular Formula: C₁₂H₉N₃O
• Molecular Weight: 211.22
• CAS Registry Number: 78415-72-2
• EC Number: 278-903-6
• SMILES: CC1=C(C=C(C(=O)N1)C#N)C2=CC=NC=C2

Properties

• Solubility: >10 mg/mL (DMSO), Insoluble (water)

Safety Data

• Hazard Symbols: GHS06 Danger
• Risk Statements: H301+H311+H331-H301-H311-H331
• Safety Statements: P261-P262-P264-P270-P271-P280-P301+P316-P302+P352-P304+P340-P316-P321-P330-P361+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	3	H301
Acute toxicity	Acute Tox.	3	H311
Acute toxicity	Acute Tox.	3	H331
Eye irritation	Eye Irrit.	2	H319
Carcinogenicity	Carc.	1B	H350
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335

• Transport Information: UN 2811

Discovery and Applications

Milrinone is a potent phosphodiesterase III inhibitor that was first synthesized in the 1970s as part of an effort to develop new drugs for the treatment of cardiovascular disease. It was derived by modifying the chemical structure of another phosphodiesterase III inhibitor, amrinone, with the goal of improving its clinical efficacy and reducing adverse effects.

Milrinone, chemically known as 1,6-dihydro-2-methyl-6-oxo-[3,4'-bipyridyl]-5-carbonitrile, exerts its pharmacological effects by inhibiting the activity of the phosphodiesterase III enzyme. This inhibition results in elevated levels of cyclic adenosine monophosphate (cAMP) within cardiac and smooth muscle cells. Elevated cAMP levels lead to increased myocardial contractility (positive inotropy) and vasodilation, primarily by relaxing vascular smooth muscle.

Milrinone is primarily used to treat acute and chronic heart failure, particularly when conventional treatments such as beta-blockers and angiotensin-converting enzyme inhibitors are inadequate or contraindicated. Its dual action as an inotrope and vasodilator helps improve cardiac output and relieve heart failure symptoms, such as dyspnea and fatigue.

In pediatric cardiology, milrinone is used to support cardiac function in infants and children with congenital heart defects who undergo surgery or experience an acute heart failure episode.

Ongoing studies explore other uses of milrinone in conditions such as septic shock, pulmonary hypertension, and perioperative cardiac support. Its role in improving these critical care settings is still under investigation.

Milrinone is typically administered intravenously because of its rapid onset of action and short half-life. An initial loading dose is followed by a continuous infusion to maintain therapeutic levels. Dose adjustments are often necessary based on individual patient response and clinical status.

While milrinone is generally well tolerated, it can cause side effects such as hypotension, arrhythmias, and thrombocytopenia. Close monitoring of cardiac function, blood pressure, and electrolyte levels during treatment is essential to mitigate potential risks.

Future studies are designed to optimize the therapeutic efficacy and safety of milrinone through new dosing methods and combination therapies. Advances in understanding its molecular interactions and pharmacokinetics will allow for tailored treatment options for specific patient populations.

References

2003. Role of nonglycosidic inotropic agents: indications, ethics, and limitations. The Medical clinics of North America, 87(2).
DOI: 10.1016/s0025-7125(02)00185-2

1998. Calcium Sensitising Agents in Heart Failure. Drugs & Aging, 12(3).
DOI: 10.2165/00002512-199812030-00003

1984. Oral and Intravenous Pharmacokinetics of Milrinone in Human Volunteers. Journal of Pharmaceutical Sciences, 73(10).
DOI: 10.1002/jps.2600731029