DrugBank: Milrinone (DB00235)

targets (1)

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

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Milrinone Lactate

Salts

Not Available

Brand names

Name	Company
Corotrop
Corotrope
Milrila
Primacor

Brand 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

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

solid

Experimental Properties

Property	Value	Source
melting point	>300 °C	PhysProp
water solubility	Slightly soluble	Not Available
logP	0.4	Not Available

Predicted Properties

Property	Value	Source
water solubility	2.09e-01 g/l	ALOGPS
logP	1.04	ALOGPS
logP	0.33	ChemAxon
logS	-3	ALOGPS
pKa (strongest acidic)	7.54	ChemAxon
pKa (strongest basic)	4.82	ChemAxon
physiological charge	0	ChemAxon
hydrogen acceptor count	3	ChemAxon
hydrogen donor count	1	ChemAxon
polar surface area	65.78	ChemAxon
rotatable bond count	1	ChemAxon
refractivity	61.14	ChemAxon
polarizability	21.46	ChemAxon

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Drug	D00417
KEGG Compound	C07224
PubChem Compound	4197
PubChem Substance	46507838
ChemSpider	4052
BindingDB	15296
ChEBI	50693
ChEMBL	50693
Therapeutic Targets Database	DAP000150
PharmGKB	PA164749171
Drug Product Database	2244811
RxList	http://www.rxlist.com/cgi/generic3/milrin.htm
Drugs.com	http://www.drugs.com/cdi/milrinone.html
Wikipedia	http://en.wikipedia.org/wiki/Milrinone

ATC Codes

C01CE02

AHFS Codes

24:04.08

PDB Entries

Not Available

FDA label

show (491 KB)

MSDS

show (34.8 KB)

Interactions

Drug Interactions

Not Available

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 Gene: PDE3A Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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 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 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 Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

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:

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
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
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
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
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
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 February 08, 2013 16:19