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
Potent effects of novel anti-platelet aggregatory cilostamide analogues on recombinant cyclic nucleotide phosphodiesterase isozyme activity.	2000 Feb 15	10644042
Vasopressin as an alternative to norepinephrine in the treatment of milrinone-induced hypotension.	2000 Jan	10667533
Vascular relaxant effects of toborinone on the isolated canine internal mammary artery.	2001	11759883
High calcium and dobutamine positive inotropy in the perfused mouse heart: myofilament calcium responsiveness, energetic economy, and effects of protein kinase C inhibition.	2001	11553322
Comparison of dobutamine-based and milrinone-based therapy for advanced decompensated congestive heart failure: Hemodynamic efficacy, clinical outcome, and economic impact.	2001 Dec	11717603
Slow induction of milrinone after coronary artery bypass grafting.	2001 Feb	11343562
Comparison of systemic vasodilators: effects on flow in internal mammary and radial arteries.	2001 Jan	11216733
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
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
A randomized multicenter study comparing the efficacy and safety of intravenous milrinone and intravenous nitroglycerin in patients with advanced heart failure.	2001 Jun	11420762
Sildenafil (viagra) facilitates weaning of inhaled nitric oxide following placement of a biventricular-assist device.	2001 May	11377161
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
Cell-based assay for high-throughput quantitative screening of CFTR chloride transport agonists.	2001 Nov	11600438
Effects of milrinone on left ventricular end-systolic pressure-volume relationship of rat hearts in situ.	2001 Sep	11553033
Nitric oxide-cGMP pathway facilitates acetylcholine release and bradycardia during vagal nerve stimulation in the guinea-pig in vitro.	2001 Sep 1	11533140
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
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
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
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
Effects of phosphodiesterase III inhibition on length-dependent regulation of myocardial function in coronary surgery patients.	2002 Jun	12173193
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
Treatment of acute heart failure: out with the old, in with the new.	2002 Mar 27	11911762
New mechanism of action for cilostazol: interplay between adenosine and cilostazol in inhibiting platelet activation.	2002 Oct	12352320
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 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