Scroll

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

Stem definition	Drug id	CAS RN
cardiac stimulants, amrinone derivatives	1809	78415-72-2

Description:

Molecule	Description
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

Molecule

Description

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:

Dose	Unit	Route
50	mg	P

ADMET properties:

Property	Value	Reference
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 µM/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:

Date	Agency	Company	Orphan
Dec. 31, 1987	FDA	SANOFI AVENTIS US

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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:

Source	Code	Description
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)

Disease	Relation	SNOMED_ID	DOID
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 level	Dissociation constant	Type (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:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
cGMP-inhibited 3',5'-cyclic phosphodiesterase A	Enzyme	Q14432	PDE3A_HUMAN	INHIBITOR	IC50	6.36	CHEMBL	CHEMBL
cGMP-specific 3',5'-cyclic phosphodiesterase	Enzyme	O76074	PDE5A_HUMAN		IC50	6.13	CHEMBL
cGMP-inhibited 3',5'-cyclic phosphodiesterase B	Enzyme	Q13370	PDE3B_HUMAN		IC50	6.55	CHEMBL
Phosphodiesterase 4	Enzyme	P27815 Q07343 Q08493 Q08499	PDE4A_HUMAN PDE4B_HUMAN PDE4C_HUMAN PDE4D_HUMAN		IC50	5.22	CHEMBL
Phosphodiesterase 3	Enzyme	Q13370 Q14432	PDE3A_HUMAN PDE3B_HUMAN		Ki	6.82	CHEMBL
Cyclic nucleotide phosphodiesterase PDE3A	Enzyme		Q9XSW7_PIG		IC50	6.07	CHEMBL
Cyclic AMP-specific phosphodiesterase SSPDE4A1A	Enzyme		O77823_PIG		IC50	4.89	CHEMBL
cGMP-specific 3',5'-cyclic phosphodiesterase	Enzyme		PDE5A_BOVIN		IC50	5.30	CHEMBL
Uncharacterized protein	Enzyme		E1BN64_BOVIN		IC50	6	CHEMBL
cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Enzyme		PDE4A_CAVPO		Ki	5.33	CHEMBL

External reference:

ID	Source
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:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
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