milrinone Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
cardiac stimulants, amrinone derivatives 1809 78415-72-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • primacor
  • milrinone
  • corotrop
  • corotrope
  • milrinone lactate
A positive inotropic cardiotonic agent with vasodilator properties. It inhibits cAMP phosphodiesterase type 3 activity in myocardium and vascular smooth muscle. Milrinone is a derivative of amrinone and has 20-30 times the inotropic potency of amrinone.
  • Molecular weight: 211.22
  • Formula: C12H9N3O
  • CLOGP: -0.03
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 1
  • TPSA: 65.78
  • ALOGS: -3
  • ROTB: 1

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
50 mg P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 1 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 85 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 5.35 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 86 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.25 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 6.20 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.04 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 0.80 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Dec. 31, 1987 FDA SANOFI AVENTIS US

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Fear 185.92 40.16 56 2151 16116 46667739
Renal injury 172.32 40.16 47 2160 9494 46674361
Injury 172.16 40.16 68 2139 43959 46639896
Renal failure 162.21 40.16 87 2120 113507 46570348
Anhedonia 159.47 40.16 45 2162 10290 46673565
Multiple organ dysfunction syndrome 141.72 40.16 62 2145 51648 46632207
Unevaluable event 138.44 40.16 59 2148 46116 46637739
Emotional distress 132.53 40.16 51 2156 30656 46653199
Cardiogenic shock 99.42 40.16 35 2172 16349 46667506
Stress 80.36 40.16 42 2165 51509 46632346
Renal impairment 68.54 40.16 43 2164 74329 46609526
Anxiety 65.75 40.16 60 2147 181897 46501958
Hypotension 41.76 40.16 53 2154 232536 46451319

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Fear 247.14 37.34 74 2668 10751 29938985
Injury 226.12 37.34 82 2660 21649 29928087
Renal injury 203.54 37.34 65 2677 11664 29938072
Anhedonia 203.06 37.34 60 2682 8309 29941427
Unevaluable event 202.59 37.34 84 2658 31701 29918035
Emotional distress 165.72 37.34 60 2682 15705 29934031
Renal failure 144.58 37.34 108 2634 128858 29820878
Stress 123.72 37.34 52 2690 20183 29929553
Anxiety 106.57 37.34 78 2664 89793 29859943
Multiple organ dysfunction syndrome 86.42 37.34 60 2682 63427 29886309
Pain 78.13 37.34 87 2655 172554 29777182
Renal impairment 73.43 37.34 61 2681 84123 29865613
Cardiogenic shock 43.49 37.34 24 2718 16837 29932899
Cardiac failure 39.18 37.34 43 2699 83375 29866361

Pharmacologic Action:

SourceCodeDescription
ATC C01CE02 CARDIOVASCULAR SYSTEM
CARDIAC THERAPY
CARDIAC STIMULANTS EXCL. CARDIAC GLYCOSIDES
Phosphodiesterase inhibitors
FDA MoA N0000175086 Phosphodiesterase 3 Inhibitors
FDA EPC N0000175598 Phosphodiesterase 3 Inhibitor
MeSH PA D002316 Cardiotonic Agents
MeSH PA D002317 Cardiovascular Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D006401 Hematologic Agents
MeSH PA D058987 Phosphodiesterase 3 Inhibitors
MeSH PA D010726 Phosphodiesterase Inhibitors
MeSH PA D010975 Platelet Aggregation Inhibitors
MeSH PA D020011 Protective Agents
MeSH PA D014665 Vasodilator Agents
CHEBI has role CHEBI:35620 vasodilator
CHEBI has role CHEBI:38147 cardiotonic drugs
CHEBI has role CHEBI:50427 platelet aggregation inhibitors
CHEBI has role CHEBI:50568 cyclic nucleotide phosphodiesterase inhibitor

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Decompensated cardiac failure indication 195111005
Myocardial infarction contraindication 22298006 DOID:5844
Conduction disorder of the heart contraindication 44808001
Low blood pressure contraindication 45007003
Pulmonic valve stenosis contraindication 56786000 DOID:6420
Kidney disease contraindication 90708001 DOID:557
Idiopathic hypertrophic subaortic stenosis contraindication 360465008

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 6.97 acidic
pKa2 6.24 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
cGMP-inhibited 3',5'-cyclic phosphodiesterase A Enzyme INHIBITOR IC50 6.36 CHEMBL CHEMBL
cGMP-specific 3',5'-cyclic phosphodiesterase Enzyme IC50 6.13 CHEMBL
cGMP-inhibited 3',5'-cyclic phosphodiesterase B Enzyme IC50 6.55 CHEMBL
Phosphodiesterase 4 Enzyme IC50 5.22 CHEMBL
Phosphodiesterase 3 Enzyme Ki 6.82 CHEMBL
Cyclic nucleotide phosphodiesterase PDE3A Enzyme IC50 6.07 CHEMBL
Cyclic AMP-specific phosphodiesterase SSPDE4A1A Enzyme IC50 4.89 CHEMBL
cGMP-specific 3',5'-cyclic phosphodiesterase Enzyme IC50 5.30 CHEMBL
Uncharacterized protein Enzyme IC50 6 CHEMBL
cAMP-specific 3',5'-cyclic phosphodiesterase 4A Enzyme Ki 5.33 CHEMBL

External reference:

IDSource
4023601 VUID
N0000021606 NUI
D00417 KEGG_DRUG
100286-97-3 SECONDARY_CAS_RN
4020722 VANDF
4023601 VANDF
C1563869 UMLSCUI
CHEBI:50693 CHEBI
MIL PDB_CHEM_ID
CHEMBL189 ChEMBL_ID
CHEMBL1200977 ChEMBL_ID
D020105 MESH_DESCRIPTOR_UI
DB00235 DRUGBANK_ID
4197 PUBCHEM_CID
5225 IUPHAR_LIGAND_ID
5383 INN_ID
JU9YAX04C7 UNII
155120 RXNORM
43671 MMSL
5116 MMSL
6676 MMSL
d00302 MMSL
004083 NDDF
004084 NDDF
108480007 SNOMEDCT_US
108481006 SNOMEDCT_US
373441005 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Milrinone Lactate HUMAN PRESCRIPTION DRUG LABEL 1 0143-9326 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 23 sections
Milrinone Lactate HUMAN PRESCRIPTION DRUG LABEL 1 0143-9373 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 19 sections
Milrinone Lactate HUMAN PRESCRIPTION DRUG LABEL 1 0143-9374 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 19 sections
Milrinone Lactate HUMAN PRESCRIPTION DRUG LABEL 1 0143-9708 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 25 sections
Milrinone Lactate HUMAN PRESCRIPTION DRUG LABEL 1 0143-9709 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 25 sections
Milrinone Lactate HUMAN PRESCRIPTION DRUG LABEL 1 0143-9710 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 25 sections
Milrinone Lactate in Dextrose HUMAN PRESCRIPTION DRUG LABEL 1 0143-9718 INJECTION, SOLUTION 200 ug INTRAVENOUS ANDA 21 sections
Milrinone Lactate in Dextrose HUMAN PRESCRIPTION DRUG LABEL 1 0143-9719 INJECTION, SOLUTION 200 ug INTRAVENOUS ANDA 21 sections
Milrinone Lactate in Dextrose HUMAN PRESCRIPTION DRUG LABEL 1 0338-6010 INJECTION, SOLUTION 0.20 mg INTRAVENOUS ANDA 23 sections
Milrinone Lactate in Dextrose HUMAN PRESCRIPTION DRUG LABEL 1 0338-6011 INJECTION, SOLUTION 0.20 mg INTRAVENOUS ANDA 23 sections
MILRINONE LACTATE HUMAN PRESCRIPTION DRUG LABEL 1 0409-0212 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 11 sections
Milrinone Lactate HUMAN PRESCRIPTION DRUG LABEL 1 0409-2776 INJECTION, SOLUTION 200 ug INTRAVENOUS ANDA 25 sections
Milrinone Lactate HUMAN PRESCRIPTION DRUG LABEL 1 0641-6065 INJECTION 1 mg INTRAVENOUS ANDA 25 sections
Milrinone Lactate HUMAN PRESCRIPTION DRUG LABEL 1 0641-6067 INJECTION 1 mg INTRAVENOUS ANDA 25 sections
Milrinone Lactate in Dextrose HUMAN PRESCRIPTION DRUG LABEL 1 25021-313 INJECTION, SOLUTION 0.20 mg INTRAVENOUS ANDA 23 sections
Milrinone Lactate Human Prescription Drug Label 1 55150-287 INJECTION, SOLUTION 0.20 mg INTRAVENOUS ANDA 21 sections
Milrinone Lactate Human Prescription Drug Label 1 55150-288 INJECTION, SOLUTION 0.20 mg INTRAVENOUS ANDA 21 sections
Milrinone Lactate Human Prescription Drug Label 1 63323-617 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 11 sections
Milrinone Lactate Human Prescription Drug Label 1 65145-120 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 18 sections
Milrinone Lactate Human Prescription Drug Label 1 65145-121 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 18 sections
Milrinone Lactate Human Prescription Drug Label 1 65145-122 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 18 sections
Milrinone Lactate Human Prescription Drug Label 1 68083-318 INJECTION 1 mg INTRAVENOUS ANDA 22 sections
Milrinone Lactate in Dextrose Human Prescription Drug Label 1 68083-410 INJECTION, SOLUTION 0.20 mg INTRAVENOUS ANDA 19 sections
Milrinone Lactate in Dextrose Human Prescription Drug Label 1 68083-411 INJECTION, SOLUTION 0.20 mg INTRAVENOUS ANDA 19 sections
Milrinone Lactate HUMAN PRESCRIPTION DRUG LABEL 1 71288-200 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 23 sections