Details of the Drug

General Information of Drug (ID: DM8TUPF)

Drug Name

Milrinone

Synonyms

Corotrop; Corotrope; Milrila; Milrinona; Milrinonum; Primacor; Milrinona [Spanish]; Milrinonum [Latin]; M 4659; M1663; YM 018; MILRINONE LACTATE IN DEXTROSE 5% IN PLASTIC CONTAINER; Milrila (TN); PRIMACOR IN DEXTROSE 5% IN PLASTIC CONTAINER; Primacor (TN); WIN 47203-2; Win-47203; Milrinone [USAN:BAN:INN]; Win-47203-2; Milrinone (JAN/USAN/INN); 1,6-Dihydro-2-methyl-6-oxo(3,4'-bipyridine)-5-carbonitrile; 1,6-Dihydro-2-methyl-6-oxo-(3,4′-bipyridine)-5-carbonitrile; 1,6-Dihydro-2-methyl-6-oxo-(3,4'-bipyridine)-5-carbonitrile; 1,6-Dihydro-2-methyl-6-oxo-3,4-bipyridine-5-carbonitrile; 1,6-Dihydro-2-methyl-6-oxo-[3,4'-bipyridine]-5-carbonitrile; 111GE027; 2-methyl-6-oxo-1,6-dihydro-3,4'-bipyridine-5-carbonitrile; 3-Cyano-6-methyl-5-(4-pyridyl)-2-pyridone; 6-Methyl-5-(4-pyridyl)-2-pyridone-3-carbonitrile; 6-methyl-2-oxo-5-pyridin-4-yl-1H-pyridine-3-carbonitrile

Indication

Disease Entry	ICD 11	Status	REF
Congestive heart failure	BD10	Approved	[1], [2]

Therapeutic Class

Cardiotonic Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

211.22

Topological Polar Surface Area (xlogp)

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [3]
Bioavailability: 86% of drug becomes completely available to its intended biological destination(s) [4]
Clearance: The clearance of drug is 0.13 L/h/kg [5]
Elimination: Milrinone is primarily excreted in the urine, with 60% of a dose recovered after two hours and 90% within eight hours [6]
Half-life: The concentration or amount of drug in body reduced by one-half in 2.3 hours (injections between 12.5 - 125 g/kg), and 2.4 hours (infusions between 0.2 - 0.7 g/kg/minutes) [5]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 5.35 micromolar/kg/day [7]
Unbound Fraction: The unbound fraction of drug in plasma is 0.035% [8]
Vd: The volume of distribution (Vd) of drug is 0.38 L/kg [5]
Water Solubility: The ability of drug to dissolve in water is measured as 1 mg/mL [3]

Chemical Identifiers

Formula: C12H9N3O
IUPAC Name: 6-methyl-2-oxo-5-pyridin-4-yl-1H-pyridine-3-carbonitrile
Canonical SMILES: CC1=C(C=C(C(=O)N1)C#N)C2=CC=NC=C2
InChI: 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)
InChIKey: PZRHRDRVRGEVNW-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 4197
ChEBI ID: CHEBI:50693
CAS Number: 78415-72-2
DrugBank ID: DB00235
TTD ID: D0Y9ZE

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Phosphodiesterase 3 (PDE3)	TTZCG4L	NOUNIPROTAC	Modulator	[9]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Milrinone (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Linezolid	DMGFPU2	Moderate	Additive hypotensive effects by the combination of Milrinone and Linezolid.	Bacterial infection [1A00-1C4Z]	[18]
Selegiline	DM6034S	Moderate	Additive hypotensive effects by the combination of Milrinone and Selegiline.	Depression [6A70-6A7Z]	[18]
Isocarboxazid	DMAF1NB	Moderate	Additive hypotensive effects by the combination of Milrinone and Isocarboxazid.	Depression [6A70-6A7Z]	[18]
Tranylcypromine	DMGB5RE	Moderate	Additive hypotensive effects by the combination of Milrinone and Tranylcypromine.	Depression [6A70-6A7Z]	[19]
Phenelzine	DMHIDUE	Moderate	Additive hypotensive effects by the combination of Milrinone and Phenelzine.	Depression [6A70-6A7Z]	[18]
Procarbazine	DMIK367	Moderate	Additive hypotensive effects by the combination of Milrinone and Procarbazine.	Hodgkin lymphoma [2B30]	[18]
Ozanimod	DMT6AM2	Moderate	Additive hypotensive effects by the combination of Milrinone and Ozanimod.	Multiple sclerosis [8A40]	[18]
Safinamide	DM0YWJC	Moderate	Additive hypotensive effects by the combination of Milrinone and Safinamide.	Parkinsonism [8A00]	[18]
Rasagiline	DM3WKQ4	Moderate	Additive hypotensive effects by the combination of Milrinone and Rasagiline.	Parkinsonism [8A00]	[18]
Disopyramide	DM5SYZP	Moderate	Additive hypotensive effects by the combination of Milrinone and Disopyramide.	Ventricular tachyarrhythmia [BC71]	[20]
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⏷ Show the Full List of 10 DDI Information of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5225).
2	Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
3	BDDCS applied to over 900 drugs
4	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
5	FDA Approved Drug Products: PRIMACOR (milrinone) injection
6	Shipley JB, Tolman D, Hastillo A, Hess ML: Milrinone: basic and clinical pharmacology and acute and chronic management. Am J Med Sci. 1996 Jun;311(6):286-91. doi: 10.1097/00000441-199606000-00011.
7	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
8	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
9	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
10	Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond. Nat Rev Drug Discov. 2019 Oct;18(10):770-796.
11	In vitro and in vivo effects of the phosphodiesterase-III inhibitor enoximone on malignant hyperthermia-susceptible swine. Anesthesiology. 2003 Apr;98(4):944-9.
12	Olprinone: a phosphodiesterase III inhibitor with positive inotropic and vasodilator effects. Cardiovasc Drug Rev. 2002 Fall;20(3):163-74.
13	Effects of amrinone on hepatic ischemia-reperfusion injury in rats. J Hepatol. 2002 Jul;37(1):31-8.
14	The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. J Neural Transm (Vienna). 2010 Nov;117(11):1319-25.
15	Company report (MediciNova)
16	Efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trials.Lancet Respir Med.2013 Nov;1(9):714-27.
17	Effects of the positive inotropic agent Org 30029 on developed force and aequorin light transients in intact canine ventricular myocardium. Circ Res. 1993 Mar;72(3):597-606.
18	Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6. [PMID: 1116424]
19	Product Information. Marplan (isocarboxazid) Roche Laboratories, Nutley, NJ.
20	Product Information. Inocor (inamrinone). Sanofi Winthrop Pharmaceuticals, New York, NY.