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

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

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
Hemodynamic effects of milrinone during weaning from cardiopulmonary bypass: comparison of patients with a low and high prebypass cardiac index.	2000 Aug	10972598
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
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
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
Physiological increase in plasma leptin markedly inhibits insulin secretion in vivo.	2001 Feb	11272146
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
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
Inhibitory effects of cyclic AMP elevating agents on lipopolysaccharide (LPS)-induced microvascular permeability change in mouse skin.	2001 May	11350859
Improved survival with simendan after experimental myocardial infarction in rats.	2001 May 11	11426847
Discriminative stimulus effects of the type-4 phosphodiesterase inhibitor rolipram in rats.	2001 Nov	11713620
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
Assessment of cardiovascular dynamics by pressure-area relations in pediatric patients with congenital heart disease.	2001 Sep	11547307
Carvedilol titration in patients with congestive heart failure receiving inotropic therapy.	2001 Sep	11526366
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
Phosphodiesterase 3 inhibitors selectively block the spontaneous resumption of meiosis by macaque oocytes in vitro.	2002 Aug	12151440
Intravenous milrinone in cardiac surgery.	2002 Jan	11834047
Assessing the emetic potential of PDE4 inhibitors in rats.	2002 Jan	11786486
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
22nd International Symposium on Intensive Care and Emergency Medicine, Brussels, Belgium, 19-22 March 2002.	2002 Jun	12133191
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
Differential regulation of human platelet responses by cGMP inhibited and stimulated cAMP phosphodiesterases.	2002 May	12038792
Effects of cAMP modulators on long-chain fatty-acid uptake and utilization by electrically stimulated rat cardiac myocytes.	2002 Nov 1	12093365

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 16:11:59 GMT 2023` Edited by `admin` on `Fri Dec 15 16:11:59 GMT 2023`
Record UNII	JU9YAX04C7
Record Status	`Validated (UNII)`
Record Version

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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