MILRINONE

First approved in 1987

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H9N3O
Molecular Weight	211.2194
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=C(C=C(C#N)C(=O)N1)C2=CC=NC=C2

InChI

InChIKey=PZRHRDRVRGEVNW-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00235
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/cdi/milrinone.html

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. 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. Milrinone is indicated for the treatment of congestive heart failure. Milrinone was marketed under the brand name Primacor.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Phosphodiesterase 3A 7 Target ID: CHEMBL241 Sources: http://www.drugbank.ca/drugs/DB00235	Inhibitor 8297		0.45 µM [IC50]
Phosphodiesterase 3B 8 Target ID: CHEMBL290 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10644042	Inhibitor 8297		1.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acute decompensated heart failure 3 Sources: https://www.drugs.com/pro/milrinone.html	Primary		Approved 8429	Milrinone Lactate Approved Use Milrinone lactate injection is indicated for the short-term intravenous treatment of patients with acute decompensated heart failure. Launch Date 1.02245761E12

C_max

Value	Dose	Co-administered	Analyte	Population
162 μg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3053125	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		MILRINONE plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
454 μg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3053125	75 μg/kg bw single, intravenous dose: 75 μg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered:		MILRINONE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1.749 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7728786	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		MILRINONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
439 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7728786	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		MILRINONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
1.92 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7728786	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	MILRINONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.758 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7728786	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	MILRINONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.94 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3053125	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	MILRINONE plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
1.7 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3053125	75 μg/kg bw single, intravenous dose: 75 μg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered:	MILRINONE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/17146843/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:50693	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:50693
MolPort	MolPort-003-666-840	https://www.molport.com/shop/molecule-link/MolPort-003-666-840
MolPort	MolPort-006-138-878	https://www.molport.com/shop/molecule-link/MolPort-006-138-878
Selleck Chemicals	Milrinone(Primacor)	http://www.selleckchem.com/products/Milrinone(Primacor).html
ZINC	ZINC000009224016	http://zinc15.docking.org/substances/ZINC000009224016
eMolecules	591956	https://www.emolecules.com/cgi-bin/more?vid=591956

PubMed

Title	Date	PubMed
Vascular relaxant effects of toborinone on the isolated canine internal mammary artery.	2001	11759883
Identification and functional study of phosphodiesterases in rat urinary bladder.	2001 Dec	11828991
[The pulmonary vasodilatory effect of inhaled prostacyclin and milrinone in heart].	2001 Dec	11792300
Comparison of milrinone versus nitroglycerin, alone and in combination, on grafted internal mammary artery flow after cardiopulmonary bypass: effects of alpha-adrenergic stimulation.	2001 Dec	11748520
Milrinone versus dobutamine in heart failure subjects treated chronically with carvedilol.	2001 Dec	11744130
Inhibition of cyclic-3',5'-nucleotide phosphodiesterase abrogates the synergism of hypoxia with lipopolysaccharide in the induction of macrophage TNF-alpha production.	2001 Dec	11735278
Mouse oocyte mitogenic activity is developmentally coordinated throughout folliculogenesis and meiotic maturation.	2001 Dec 1	11784064
Cilostazol (pletal): a dual inhibitor of cyclic nucleotide phosphodiesterase type 3 and adenosine uptake.	2001 Winter	11830753
Modulation of TNF and GM-CSF release from dispersed human nasal polyp cells and human whole blood by inhibitors of different PDE isoenzymes and glucocorticoids.	2002	11969359
Positive inotropic drug infusions for patients with heart failure: current controversies and best practice.	2002 Apr	11984193
Differential effects of specific phosphodiesterase isoenzyme inhibitors on bovine oocyte meiotic maturation.	2002 Apr 15	11944932
The effectiveness and relative effectiveness of intravenous inotropic drugs acting through the adrenergic pathway in patients with heart failure-a meta-regression analysis.	2002 Aug	12167393
Phosphodiesterase 3 inhibitors selectively block the spontaneous resumption of meiosis by macaque oocytes in vitro.	2002 Aug	12151440
Acute renal failure secondary to milrinone in a patient with cardiac amyloidosis.	2002 Aug	12148128
Presence of cyclic nucleotide phosphodiesterases PDE1A, existing as a stable complex with calmodulin, and PDE3A in human spermatozoa.	2002 Aug	12135876
Nitric oxide signalling by selective beta(2)-adrenoceptor stimulation prevents ACh-induced inhibition of beta(2)-stimulated Ca(2+) current in cat atrial myocytes.	2002 Aug 1	12154173
[Reversible cardiomyopathy secondary to interferon-alpha in chronic myelogenous leukemia].	2002 Feb	11865642
Milrinone increases middle cerebral artery blood flow velocity after cardiopulmonary bypass.	2002 Feb	11854881
Involvement of phosphodiesterase isozymes in osteoblastic differentiation.	2002 Feb	11811555
Intravenous milrinone in cardiac surgery.	2002 Jan	11834047
Effects of milrinone for right ventricular failure after left ventricular assist device implantation.	2002 Jan	11833845
Assessing the emetic potential of PDE4 inhibitors in rats.	2002 Jan	11786486
Prophylactic intravenous use of milrinone after cardiac operation in pediatrics (PRIMACORP) study. Prophylactic Intravenous Use of Milrinone After Cardiac Operation in Pediatrics.	2002 Jan	11773907
The efficacy of preemptive Milrinone or Amrinone therapy in patients undergoing coronary artery bypass grafting.	2002 Jan	11772795
Effect of type 3 and type 4 phosphodiesterase inhibitors on the maintenance of bovine oocytes in meiotic arrest.	2002 Jan	11751280
Cyclic AMP-dependent Cl secretion is regulated by multiple phosphodiesterase subtypes in human colonic epithelial cells.	2002 Jan 15	11891572
Activation of protein kinase A by nitric oxide in cultured dorsal root ganglion neurites of the rat, examined by a fluorescence probe, ARII.	2002 Jan 18	11786215
[Pharmacology of inotropic agents].	2002 Jan-Mar	12001837
Mechanisms of leptin secretion from white adipocytes.	2002 Jul	12055093
Levosimendan: a unique approach to the treatment of heart failure.	2002 Jul-Aug	12147186
Effects of phosphodiesterase III inhibition on length-dependent regulation of myocardial function in coronary surgery patients.	2002 Jun	12173193
22nd International Symposium on Intensive Care and Emergency Medicine, Brussels, Belgium, 19-22 March 2002.	2002 Jun	12133191
Recently published papers: topical issues in pharmacology.	2002 Jun	12133177
Effects of milrinone on hemodynamics and regional blood flow in the hypoxic dog.	2002 Jun	12130834
Cardiac performance during vasopressin infusion in postcardiotomy shock.	2002 Jun	12107681
Physical compatibility of milrinone lactate injection with intravenous drugs commonly used in the pediatric intensive care unit.	2002 Mar 1	11887412
Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial.	2002 Mar 27	11911756
Differential regulation of human platelet responses by cGMP inhibited and stimulated cAMP phosphodiesterases.	2002 May	12038792
Novel use of a short-acting intravenous beta blocker in combination with inotropic therapy as a bridge to chronic oral beta blockade in patients with advanced heart failure.	2002 May	12018885
A potential role for AMP-activated protein kinase in meiotic induction in mouse oocytes.	2002 May 1	11969266
Control of renin secretion from rat juxtaglomerular cells by cAMP-specific phosphodiesterases.	2002 May 17	12016266
Relaxation induced by milrinone and rolipram in human penile arteries and veins.	2002 May 24	12191588
Effects of cAMP modulators on long-chain fatty-acid uptake and utilization by electrically stimulated rat cardiac myocytes.	2002 Nov 1	12093365
New mechanism of action for cilostazol: interplay between adenosine and cilostazol in inhibiting platelet activation.	2002 Oct	12352320
Lipopolysaccharide-induced acute renal failure in conscious rats: effects of specific phosphodiesterase type 3 and 4 inhibition.	2002 Oct	12235272
Megadose of milrinone as an alternative to extracorporeal membrane oxygenation for treatment of graft failure early after cardiac transplantation.	2002 Sep	12202888
Potentiation of slow component of delayed rectifier K(+) current by cGMP via two distinct mechanisms: inhibition of phosphodiesterase 3 and activation of protein kinase G.	2002 Sep	12183338
Identification of interaction sites of cyclic nucleotide phosphodiesterase type 3A with milrinone and cilostazol using molecular modeling and site-directed mutagenesis.	2002 Sep	12181427
Exhaled nitric oxide: a marker of pulmonary hemodynamics in heart failure.	2002 Sep 18	12354437
Subtype-specific roles of cAMP phosphodiesterases in regulation of atrial natriuretic peptide release.	2002 Sep 20	12242091

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Congestive Heart Failure Loading dose: 50 mcg/kg IV over 10 minutes. Maintenance infusion: 0.375 to 0.75 mcg/kg/min.

Route of Administration: Intravenous

In Vitro Use Guide

Milrinone caused the human thoracic artery samples to relax at 10⁻⁴ M concentrations by 44%, when the external Ca²⁺ corresponded to the physiological standard.

Name

Type

Language

MILRINONE

Official Name

English

Milrinone [WHO-DD]

Common Name

English

MILRILA

Brand Name

English

MILRINONE [USP-RS]

Common Name

English

WIN 47,203-2

Code

English

MILRINONE [USAN]

Common Name

English

MILRINONE [JAN]

Common Name

English

WIN-47203-2

Code

English

MILRINONE [USP MONOGRAPH]

Common Name

English

MILRINONE [MI]

Common Name

English

milrinone [INN]

Common Name

English

MILRINONE [VANDF]

Common Name

English

NSC-760072

Code

English

MILRINONE [MART.]

Common Name

English

(3,4'-BIPYRIDINE)-5-CARBONITRILE, 1,6-DIHYDRO-2-METHYL-6-OXO-

Systematic Name

English

1,6-DIHYDRO-2-METHYL-6-OXO(3,4'-BIPYRIDINE)-5-CARBONITRILE

Systematic Name

English

Classification Tree Code System Code

NDF-RT

N0000175598