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Identification
Name Milrinone
Accession Number DB00235 (APRD00010)
Type small molecule
Groups approved
Description

A positive inotropic cardiotonic agent with vasodilator properties. It inhibits cAMP phosphodiesterase activity in myocardium and vascular smooth muscle. Milrinone is a derivative of amrinone and has 20-30 times the ionotropic potency of amrinone. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Milrinone Lactate
Brand names
  • Corotrop
  • Corotrope
  • Milrila
  • Primacor
Brand name mixtures Not Available
Categories
  • Vasodilator Agents
  • Platelet Aggregation Inhibitors
  • Phosphodiesterase Inhibitors
  • Cardiotonic Agents
CAS number 78415-72-2
Weight Average: 211.2194
Monoisotopic: 211.074561925
Chemical Formula C12H9N3O
InChI Key InChIKey=PZRHRDRVRGEVNW-UHFFFAOYSA-N
InChI
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)
Plain Text
IUPAC Name
6-methyl-2-oxo-5-(pyridin-4-yl)-1,2-dihydropyridine-3-carbonitrile
SMILES
CC1=C(C=C(C#N)C(=O)N1)C1=CC=NC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Pyridines and Derivatives
  • Pyridines
Substructures
  • Pyridines and Derivatives
  • Nitriles and Derivatives
  • Cyanides
  • Pyridines
  • Heterocyclic compounds
  • Aromatic compounds
  • Imines
Pharmacology
Indication Indicated for the treatment of congestive heart failure.
Pharmacodynamics Milrinone, a synthetic dimethylxanthine derivative structurally related to theophylline and caffeine, is used in the treatment of peripheral vascular diseases and in the management of cerebrovascular insufficiency, sickle cell disease, and diabetic neuropathy.
Mechanism of action Milrinone inhibits erythrocyte phosphodiesterase, resulting in an increase in erythrocyte cAMP activity. Subsequently, the erythrocyte membrane becomes more resistant to deformity. Along with erythrocyte activity, Milrinone also decreases blood viscosity by reducing plasma fibrinogen concentrations and increasing fibrinolytic activity.
Absorption Milrinone is rapidly and almost completely absorbed after oral administration. Bioavailability is 92% (in healthy volunteers).
Volume of distribution
  • 0.38 liters/kg [intravenous injections of 12.5 mcg/kg to 125 mcg/kg to congestive heart failure patients]
  • 0.45 liters/kg [intravenous infusions of 0.20 mcg/kg/min to 0.70 mcg/kg/min to congestive heart failure patients]
Protein binding 70 to 80%
Metabolism

There are five metabolites but the O-glucuronide represents the major pathway of biotransformation.
Route of elimination The primary route of excretion of milrinone in man is via the urine.
Half life 2.3 hours
Clearance
  • 0.13 L/kg/hr [congestive heart failure patients, following IV injections of 12.5 mcg/kg to 125 mcg/kg]
  • 0.14 L/kg/hr [congestive heart failure patients, following infusions of 0.2 mcg/kg/min to 0.7 mcg/kg/min]
Toxicity LD50 = 0.3 mg/L in rats
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • App pharmaceuticals llc
  • Baxter healthcare corp anesthesia and critical care
  • Baxter healthcare corp anesthesia critical care
  • Bedford laboratories div ben venue laboratories inc
  • Bioniche pharma usa llc
  • Claris lifesciences ltd
  • Gland pharma ltd
  • Hospira inc
  • International medicated systems ltd
  • B braun medical inc
  • Baxter healthcare corp
  • Bedford laboratories
  • Hikma farmaceutica (portugal) sa
  • Sanofi aventis us llc
Packagers
Dosage forms
Form Route Strength
Liquid Intravenous
Solution Intravenous
Prices
Unit description Cost Unit
Primacor 0.2 mg/ml-d5w 100 ml 1.6 USD ml
Milrinone-d5w 20 mg/100 ml 1.45 USD ml
Milrinone lact 20 mg/20 ml vial 1.44 USD ml
Milrinone lact 10 mg/10 ml vial 1.31 USD ml
Patents Not Available
Properties
State solid
Melting point >300 oC
Experimental Properties
Property Value Source
water solubility Slightly soluble PhysProp
logP 0.4 PhysProp
Predicted Properties
Property Value Source
water solubility 2.09e-01 g/l ALOGPS
logP 1.04 ALOGPS
logP 0.33 ChemAxon Molconvert
logS -3.00 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 65.78 ChemAxon Molconvert
rotatable bond count 1 ChemAxon Molconvert
refractivity 61.14 ChemAxon Molconvert
polarizability 21.46 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00417 Link_out
KEGG Compound C07224 Link_out
PubChem Compound 4197 Link_out
PubChem Substance 46507838 Link_out
ChemSpider 4052 Link_out
BindingDB 15296 Link_out
ChEBI 50693 Link_out
ChEMBL 50693 Link_out
Therapeutic Targets Database DAP000150 Link_out
PharmGKB PA450510 Link_out
Drug Product Database 2244811 Link_out
RxList http://www.rxlist.com/cgi/generic3/milrin.htm Link_out
Drugs.com http://www.drugs.com/cdi/milrinone.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Milrinone Link_out
ATC Codes
  • C01CE02
AHFS Codes
  • 24:04.08
PDB Entries Not Available
FDA label show (490.7 KB)
MSDS show (34.8 KB)
Interactions
Drug Interactions
Drug Interaction
Food Interactions Not Available
Targets

1. cGMP-inhibited 3',5'-cyclic phosphodiesterase A

Pharmacological action: yes
Actions: inhibitor

Hydrolyzes both cyclic AMP (cAMP) and cyclic GMP (cGMP)

Organism class: human
UniProt ID: Q14432 Link_out
Gene: PDE3A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. Kuthe A, Magert H, Uckert S, Forssmann WG, Stief CG, Jonas U: Gene expression of the phosphodiesterases 3A and 5A in human corpus cavernosum penis. Eur Urol. 2000 Jul;38(1):108-14. Pubmed
  3. Lefievre L, de Lamirande E, Gagnon C: Presence of cyclic nucleotide phosphodiesterases PDE1A, existing as a stable complex with calmodulin, and PDE3A in human spermatozoa. Biol Reprod. 2002 Aug;67(2):423-30. Pubmed
  4. Zhang W, Ke H, Colman RW: Identification of interaction sites of cyclic nucleotide phosphodiesterase type 3A with milrinone and cilostazol using molecular modeling and site-directed mutagenesis. Mol Pharmacol. 2002 Sep;62(3):514-20. Pubmed
  5. 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. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:02

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.