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

Molecular Formula	C12H9N3O
Molecular Weight	211.2194
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C3H6O3
Molecular Weight	90.0779
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

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
Potent effects of novel anti-platelet aggregatory cilostamide analogues on recombinant cyclic nucleotide phosphodiesterase isozyme activity.	2000 Feb 15	10644042
Identification and functional study of phosphodiesterases in rat urinary bladder.	2001 Dec	11828991
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
Pharmacodynamic effects of milrinone with and without a bolus loading infusion.	2001 Feb	11174341
Comparison of systemic vasodilators: effects on flow in internal mammary and radial arteries.	2001 Jan	11216733
[Effect of colforsin daropate hydrochloride after cardiopulmonary bypass].	2001 Jan	11211758
Experimental study of a type 3 phosphodiesterase inhibitor on liver graft function.	2001 Jan	11136311
Surgical issues in heart failure: what's new?	2001 Jun	11605162
Inotropes and beta-blockers: is there a need for new guidelines?	2001 Jun	11605160
Modulation of thapsigargin-induced calcium mobilisation by cyclic AMP-elevating agents in human lymphocytes is insensitive to the action of the protein kinase A inhibitor H-89.	2001 Jun	11384843
Inhibition of phosphodiesterase type III before aortic cross-clamping preserves intramyocardial cyclic adenosine monophosphate during cardiopulmonary bypass.	2001 Jun	11375808
Sildenafil (viagra) facilitates weaning of inhaled nitric oxide following placement of a biventricular-assist device.	2001 May	11377161
Inhibitory effects of cyclic AMP elevating agents on lipopolysaccharide (LPS)-induced microvascular permeability change in mouse skin.	2001 May	11350859
Discriminative stimulus effects of the type-4 phosphodiesterase inhibitor rolipram in rats.	2001 Nov	11713620
Synergistic interaction of diazepam with 3',5'-cyclic adenosine monophosphate-elevating agents on rat aortic rings.	2001 Oct 5	11675045
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
Differential effects of specific phosphodiesterase isoenzyme inhibitors on bovine oocyte meiotic maturation.	2002 Apr 15	11944932
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
Effects of milrinone for right ventricular failure after left ventricular assist device implantation.	2002 Jan	11833845
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
Levosimendan: a unique approach to the treatment of heart failure.	2002 Jul-Aug	12147186
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
Treatment of acute heart failure: out with the old, in with the new.	2002 Mar 27	11911762
Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial.	2002 Mar 27	11911756
A potential role for AMP-activated protein kinase in meiotic induction in mouse oocytes.	2002 May 1	11969266
Relaxation induced by milrinone and rolipram in human penile arteries and veins.	2002 May 24	12191588
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
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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:24:31 GMT 2023` Edited by `admin` on `Fri Dec 15 16:24:31 GMT 2023`
Record UNII	9K8XR81MO8
Record Status	`Validated (UNII)`
Record Version

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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