MILRINONE LACTATE

First approved in 1987

Details

Stereochemistry	UNKNOWN
Molecular Formula	C12H9N3O.C3H6O3
Molecular Weight	301.2973
Optical Activity	UNSPECIFIED
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=VWUPWEAFIOQCGF-UHFFFAOYSA-N

InChI=1S/C12H9N3O.C3H6O3/c1-8-11(9-2-4-14-5-3-9)6-10(7-13)12(16)15-8;1-2(4)3(5)6/h2-6H,1H3,(H,15,16);2,4H,1H3,(H,5,6)

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 2002

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
The use of milrinone in pre-transplant assessment of patients with congestive heart failure and pulmonary hypertension.	1999 Apr	10226902
[The effects of intravenous milrinone for the patient undergoing CABG].	2000 Feb	10667021
Vasopressin in the treatment of milrinone-induced hypotension in severe heart failure.	2000 Feb 15	10728962
Vasopressin as an alternative to norepinephrine in the treatment of milrinone-induced hypotension.	2000 Jan	10667533
[The effects of milrinone on hemodynamics in patients undergoing cardiac surgery].	2001 Apr	11345746
Milrinone for the treatment of cerebral vasospasm after subarachnoid hemorrhage: report of seven cases.	2001 Apr	11322432
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
The additive pulmonary vasodilatory effects of inhaled prostacyclin and inhaled milrinone in postcardiac surgical patients with pulmonary hypertension.	2001 Dec	11726420
Comparison of dobutamine-based and milrinone-based therapy for advanced decompensated congestive heart failure: Hemodynamic efficacy, clinical outcome, and economic impact.	2001 Dec	11717603
Natriuretic peptides like NO facilitate cardiac vagal neurotransmission and bradycardia via a cGMP pathway.	2001 Dec	11709398
Mouse oocyte mitogenic activity is developmentally coordinated throughout folliculogenesis and meiotic maturation.	2001 Dec 1	11784064
Slow induction of milrinone after coronary artery bypass grafting.	2001 Feb	11343562
Pharmacodynamic effects of milrinone with and without a bolus loading infusion.	2001 Feb	11174341
[Effect of colforsin daropate hydrochloride after cardiopulmonary bypass].	2001 Jan	11211758
Milrinone echocardiographic viability test: a pilot study.	2001 Jul	11447411
The effects of alpha-human atrial natriuretic peptide and milrinone on pial vessels during blood-brain barrier disruption in rabbits.	2001 Jul	11429361
Surgical issues in heart failure: what's new?	2001 Jun	11605162
Dose response to nitric oxide in adult cardiac surgery patients.	2001 Jun	11435053
Comparison of the hemodynamic effects of milrinone with dobutamine in patients after cardiac surgery.	2001 Jun	11426360
Inhibition of phosphodiesterase type III before aortic cross-clamping preserves intramyocardial cyclic adenosine monophosphate during cardiopulmonary bypass.	2001 Jun	11375808
Diazepam and rolipram differentially inhibit cyclic AMP-specific phosphodiesterases PDE4A1 and PDE4B3 in the mouse.	2001 Mar 19	11267656
Improved survival with simendan after experimental myocardial infarction in rats.	2001 May 11	11426847
The role of cGMP hydrolysing phosphodiesterases 1 and 5 in cerebral artery dilatation.	2001 May 18	11412839
Synergistic interaction of diazepam with 3',5'-cyclic adenosine monophosphate-elevating agents on rat aortic rings.	2001 Oct 5	11675045
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
[Reversible cardiomyopathy secondary to interferon-alpha in chronic myelogenous leukemia].	2002 Feb	11865642
Effect of type 3 and type 4 phosphodiesterase inhibitors on the maintenance of bovine oocytes in meiotic arrest.	2002 Jan	11751280
Mechanisms of leptin secretion from white adipocytes.	2002 Jul	12055093
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
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
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
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
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 LACTATE

Common Name

English

MILRINONE LACTATE [VANDF]

Common Name

English

MILRINONE LACTATE [ORANGE BOOK]

Common Name

English

MILRINONE LACTATE [MART.]

Common Name

English

MILRINONE LACTATE [MI]

Common Name

English

PRIMACOR

Brand Name

English

Milrinone lactate [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C744