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Identification
NameAmrinone
Accession NumberDB01427
TypeSmall Molecule
GroupsApproved
DescriptionAmrinone (or inamrinone) is a type 3 pyridine phosphodiesterase inhibitor. It is used in the treatment of congestive heart failure.
Structure
Thumb
Synonyms
Amcoral
Amrinona
Amrinonum
Inamrinone
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Inocor Liq 5mg/mlliquid5 mgintravenousSanofi Canada, Inc.1984-12-312000-07-24Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AmcoralNot Available
InocorNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Amrinone lactate
ThumbNot applicableDBSALT001311
Categories
UNIIJUT23379TN
CAS number60719-84-8
WeightAverage: 187.198
Monoisotopic: 187.074561925
Chemical FormulaC10H9N3O
InChI KeyInChIKey=RNLQIBCLLYYYFJ-UHFFFAOYSA-N
InChI
InChI=1S/C10H9N3O/c11-9-5-8(6-13-10(9)14)7-1-3-12-4-2-7/h1-6H,11H2,(H,13,14)
IUPAC Name
3-amino-5-(pyridin-4-yl)-1,2-dihydropyridin-2-one
SMILES
NC1=CC(=CNC1=O)C1=CC=NC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as bipyridines and oligopyridines. These are organic compounds containing two pyridine rings linked to each other.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyridines and derivatives
Sub ClassBipyridines and oligopyridines
Direct ParentBipyridines and oligopyridines
Alternative Parents
Substituents
  • Bipyridine
  • Pyridinone
  • Dihydropyridine
  • Aminopyridine
  • Primary aromatic amine
  • Hydropyridine
  • Heteroaromatic compound
  • Lactam
  • Azacycle
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationUsed in the treatment of congestive heart failure.
PharmacodynamicsAmrinone is a positive inotropic cardiotonic with vasodilator properties, phosphodiesterase inhibitory activity, and the ability to stimulate calcium ion influx into the cardiac cell.
Mechanism of actionAmrinone is a phosphodiesterase inhibitor (PDE3), resulting in increased cAMP and cGMP which leads to an increase in the calcium influx like that caused by beta-agonists resulting in increased inotropic effect.
Related Articles
AbsorptionNot Available
Volume of distribution
  • 1.2 L/kg [normal volunteers]
Protein binding10 to 49%
Metabolism

Hepatic.

Route of eliminationThe primary route of excretion in man is via the urine as both inamrinone and several metabolites (N-glycolyl, N-acetate, O-glucuronide and N-glucuronide).
Half life5 to 8 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9522
Blood Brain Barrier+0.9525
Caco-2 permeable+0.8867
P-glycoprotein substrateNon-substrate0.6469
P-glycoprotein inhibitor INon-inhibitor0.9338
P-glycoprotein inhibitor IINon-inhibitor0.9946
Renal organic cation transporterNon-inhibitor0.9258
CYP450 2C9 substrateNon-substrate0.8642
CYP450 2D6 substrateNon-substrate0.8389
CYP450 3A4 substrateNon-substrate0.6443
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorInhibitor0.5328
CYP450 2D6 inhibitorNon-inhibitor0.9651
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorNon-inhibitor0.6534
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5933
Ames testNon AMES toxic0.8492
CarcinogenicityNon-carcinogens0.9116
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.9371 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9923
hERG inhibition (predictor II)Non-inhibitor0.7418
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Liquidintravenous5 mg
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point294-297Lesher,G.Y. and Opalka, C.J.; US. Patent 4,004,012; January 18,1977; assigned to Sterling Drug Inc. Lesher, G.Y. and Opalka, C.J.; U.S. Patent 4,107,315; August 15,1978; assigned to Sterling Drug Inc.
Predicted Properties
PropertyValueSource
Water Solubility5.6 mg/mLALOGPS
logP0.27ALOGPS
logP-0.57ChemAxon
logS-1.5ALOGPS
pKa (Strongest Acidic)11.01ChemAxon
pKa (Strongest Basic)4.87ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area68.01 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity53.89 m3·mol-1ChemAxon
Polarizability18.94 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

Lesher,G.Y. and Opalka, C.J.; US. Patent 4,004,012; January 18,1977; assigned to Sterling
Drug Inc.
Lesher, G.Y. and Opalka, C.J.; U.S. Patent 4,107,315; August 15,1978; assigned to Sterling
Drug Inc.

General ReferencesNot Available
External Links
ATC CodesC01CE01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
2-HYDROXY-1,4-NAPHTHOQUINONEThe risk or severity of adverse effects can be increased when 2-HYDROXY-1,4-NAPHTHOQUINONE is combined with Amrinone.
2-mercaptobenzothiazoleThe risk or severity of adverse effects can be increased when 2-mercaptobenzothiazole is combined with Amrinone.
AlfuzosinAlfuzosin may increase the hypotensive activities of Amrinone.
AmobarbitalThe metabolism of Amrinone can be increased when combined with Amobarbital.
AmorolfineThe risk or severity of adverse effects can be increased when Amorolfine is combined with Amrinone.
Amphotericin BThe risk or severity of adverse effects can be increased when Amphotericin B is combined with Amrinone.
AN2690The risk or severity of adverse effects can be increased when AN2690 is combined with Amrinone.
AnidulafunginThe risk or severity of adverse effects can be increased when Anidulafungin is combined with Amrinone.
ArtemetherThe risk or severity of adverse effects can be increased when Artemether is combined with Amrinone.
AtosibanThe risk or severity of adverse effects can be increased when Amrinone is combined with Atosiban.
Atracurium besylateAmrinone may increase the neuromuscular blocking activities of Atracurium besylate.
Bafilomycin A1The risk or severity of adverse effects can be increased when Bafilomycin A1 is combined with Amrinone.
BarbitalThe metabolism of Amrinone can be increased when combined with Barbital.
Benzoic AcidThe risk or severity of adverse effects can be increased when Benzoic Acid is combined with Amrinone.
BifonazoleThe risk or severity of adverse effects can be increased when Bifonazole is combined with Amrinone.
ButenafineThe risk or severity of adverse effects can be increased when Butenafine is combined with Amrinone.
ButoconazoleThe risk or severity of adverse effects can be increased when Butoconazole is combined with Amrinone.
CandicidinThe risk or severity of adverse effects can be increased when Candicidin is combined with Amrinone.
CarvedilolCarvedilol may increase the hypotensive activities of Amrinone.
CaspofunginThe risk or severity of adverse effects can be increased when Caspofungin is combined with Amrinone.
CeruleninThe risk or severity of adverse effects can be increased when Cerulenin is combined with Amrinone.
ChloroxineThe risk or severity of adverse effects can be increased when Chloroxine is combined with Amrinone.
CiclopiroxThe risk or severity of adverse effects can be increased when Ciclopirox is combined with Amrinone.
CimetidineThe serum concentration of Amrinone can be increased when it is combined with Cimetidine.
ClopidogrelThe therapeutic efficacy of Clopidogrel can be decreased when used in combination with Amrinone.
ClotrimazoleThe risk or severity of adverse effects can be increased when Clotrimazole is combined with Amrinone.
CyclosporineThe risk or severity of adverse effects can be increased when Cyclosporine is combined with Amrinone.
DapoxetineDapoxetine may increase the orthostatic hypotensive activities of Amrinone.
Decanoic AcidThe risk or severity of adverse effects can be increased when Decanoic Acid is combined with Amrinone.
DoxazosinDoxazosin may increase the hypotensive activities of Amrinone.
EconazoleThe risk or severity of adverse effects can be increased when Econazole is combined with Amrinone.
EfavirenzThe serum concentration of Amrinone can be decreased when it is combined with Efavirenz.
EfinaconazoleThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Amrinone.
FluconazoleThe serum concentration of Amrinone can be increased when it is combined with Fluconazole.
FlucytosineThe risk or severity of adverse effects can be increased when Flucytosine is combined with Amrinone.
FosphenytoinThe serum concentration of Fosphenytoin can be increased when it is combined with Amrinone.
GlyphosateThe risk or severity of adverse effects can be increased when Glyphosate is combined with Amrinone.
GriseofulvinThe risk or severity of adverse effects can be increased when Griseofulvin is combined with Amrinone.
HaloproginThe risk or severity of adverse effects can be increased when Haloprogin is combined with Amrinone.
HexetidineThe risk or severity of adverse effects can be increased when Hexetidine is combined with Amrinone.
HexobarbitalThe metabolism of Amrinone can be increased when combined with Hexobarbital.
IndoraminIndoramin may increase the hypotensive activities of Amrinone.
IsoconazoleThe risk or severity of adverse effects can be increased when Isoconazole is combined with Amrinone.
ItraconazoleThe risk or severity of adverse effects can be increased when Itraconazole is combined with Amrinone.
KetoconazoleThe risk or severity of adverse effects can be increased when Ketoconazole is combined with Amrinone.
LabetalolLabetalol may increase the hypotensive activities of Amrinone.
Magnesium hydroxideThe risk or severity of adverse effects can be increased when Amrinone is combined with Magnesium hydroxide.
Magnesium oxideThe risk or severity of adverse effects can be increased when Amrinone is combined with Magnesium oxide.
Magnesium salicylateThe risk or severity of adverse effects can be increased when Amrinone is combined with Magnesium salicylate.
Magnesium SulfateThe risk or severity of adverse effects can be increased when Amrinone is combined with Magnesium Sulfate.
MethohexitalThe metabolism of Amrinone can be increased when combined with Methohexital.
MethylphenobarbitalThe metabolism of Amrinone can be increased when combined with Methylphenobarbital.
MevastatinThe risk or severity of adverse effects can be increased when Mevastatin is combined with Amrinone.
MicafunginThe risk or severity of adverse effects can be increased when Micafungin is combined with Amrinone.
MiconazoleThe risk or severity of adverse effects can be increased when Miconazole is combined with Amrinone.
MiltefosineThe risk or severity of adverse effects can be increased when Miltefosine is combined with Amrinone.
MivacuriumAmrinone may increase the neuromuscular blocking activities of Mivacurium.
MonensinThe risk or severity of adverse effects can be increased when Monensin is combined with Amrinone.
MyxothiazolThe risk or severity of adverse effects can be increased when Myxothiazol is combined with Amrinone.
NafcillinThe metabolism of Amrinone can be increased when combined with Nafcillin.
NaftifineThe risk or severity of adverse effects can be increased when Naftifine is combined with Amrinone.
NatamycinThe risk or severity of adverse effects can be increased when Natamycin is combined with Amrinone.
NitroprussideAmrinone may increase the hypotensive activities of Nitroprusside.
NitroxolineThe risk or severity of adverse effects can be increased when Nitroxoline is combined with Amrinone.
NystatinThe risk or severity of adverse effects can be increased when Nystatin is combined with Amrinone.
OxiconazoleThe risk or severity of adverse effects can be increased when Oxiconazole is combined with Amrinone.
pafuramidineThe risk or severity of adverse effects can be increased when pafuramidine is combined with Amrinone.
PentamidineThe risk or severity of adverse effects can be increased when Pentamidine is combined with Amrinone.
PentobarbitalThe metabolism of Amrinone can be increased when combined with Pentobarbital.
PhenobarbitalThe metabolism of Amrinone can be increased when combined with Phenobarbital.
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Amrinone.
PosaconazoleThe risk or severity of adverse effects can be increased when Posaconazole is combined with Amrinone.
PrazosinPrazosin may increase the hypotensive activities of Amrinone.
PrimidoneThe metabolism of Amrinone can be increased when combined with Primidone.
RadicicolThe risk or severity of adverse effects can be increased when Radicicol is combined with Amrinone.
RapacuroniumAmrinone may increase the neuromuscular blocking activities of Rapacuronium.
Salicylhydroxamic AcidThe risk or severity of adverse effects can be increased when Salicylhydroxamic Acid is combined with Amrinone.
Salicylic acidThe risk or severity of adverse effects can be increased when Salicylic acid is combined with Amrinone.
SecobarbitalThe metabolism of Amrinone can be increased when combined with Secobarbital.
SertaconazoleThe risk or severity of adverse effects can be increased when Sertaconazole is combined with Amrinone.
SilodosinSilodosin may increase the hypotensive activities of Amrinone.
SinefunginThe risk or severity of adverse effects can be increased when Sinefungin is combined with Amrinone.
SirolimusThe risk or severity of adverse effects can be increased when Sirolimus is combined with Amrinone.
SulconazoleThe risk or severity of adverse effects can be increased when Sulconazole is combined with Amrinone.
TamsulosinTamsulosin may increase the hypotensive activities of Amrinone.
TavaboroleThe risk or severity of adverse effects can be increased when Tavaborole is combined with Amrinone.
TerazosinTerazosin may increase the hypotensive activities of Amrinone.
TerbinafineThe risk or severity of adverse effects can be increased when Terbinafine is combined with Amrinone.
TerconazoleThe risk or severity of adverse effects can be increased when Terconazole is combined with Amrinone.
ThiamylalThe metabolism of Amrinone can be increased when combined with Thiamylal.
ThiopentalThe metabolism of Amrinone can be increased when combined with Thiopental.
ThymolThe risk or severity of adverse effects can be increased when Thymol is combined with Amrinone.
TioconazoleThe risk or severity of adverse effects can be increased when Tioconazole is combined with Amrinone.
TolnaftateThe risk or severity of adverse effects can be increased when Tolnaftate is combined with Amrinone.
TrimazosinTrimazosin may increase the hypotensive activities of Amrinone.
TrimetrexateThe risk or severity of adverse effects can be increased when Trimetrexate is combined with Amrinone.
VoriconazoleThe risk or severity of adverse effects can be increased when Voriconazole is combined with Amrinone.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Metal ion binding
Specific Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.
Gene Name:
PDE4B
Uniprot ID:
Q07343
Molecular Weight:
83342.695 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Tumor necrosis factor receptor binding
Specific Function:
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs ...
Gene Name:
TNF
Uniprot ID:
P01375
Molecular Weight:
25644.15 Da
References
  1. Kumar A, Kosuri R, Kandula P, Dimou C, Allen J, Parrillo JE: Effects of epinephrine and amrinone on contractility and cyclic adenosine monophosphate generation of tumor necrosis factor alpha-exposed cardiac myocytes. Crit Care Med. 1999 Feb;27(2):286-92. [PubMed:10075051 ]
  2. Bergman MR, Kao RH, McCune SA, Holycross BJ: Myocardial tumor necrosis factor-alpha secretion in hypertensive and heart failure-prone rats. Am J Physiol. 1999 Aug;277(2 Pt 2):H543-50. [PubMed:10444479 ]
  3. Haddad JJ, Land SC, Tarnow-Mordi WO, Zembala M, Kowalczyk D, Lauterbach R: Immunopharmacological potential of selective phosphodiesterase inhibition. I. Differential regulation of lipopolysaccharide-mediated proinflammatory cytokine (interleukin-6 and tumor necrosis factor-alpha) biosynthesis in alveolar epithelial cells. J Pharmacol Exp Ther. 2002 Feb;300(2):559-66. [PubMed:11805217 ]
  4. Marx D, Tassabehji M, Heer S, Huttenbrink KB, Szelenyi I: 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. Pulm Pharmacol Ther. 2002;15(1):7-15. [PubMed:11969359 ]
  5. Giroir BP, Beutler B: Effect of amrinone on tumor necrosis factor production in endotoxic shock. Circ Shock. 1992 Mar;36(3):200-7. [PubMed:1611705 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Metal ion binding
Specific Function:
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.
Gene Name:
PDE3A
Uniprot ID:
Q14432
Molecular Weight:
124978.06 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Kobayashi T, Sugawara Y, Ohkubo T, Imamura H, Makuuchi M: Effects of amrinone on hepatic ischemia-reperfusion injury in rats. J Hepatol. 2002 Jul;37(1):31-8. [PubMed:12076859 ]
  3. Ko Y, Morita K, Nagahori R, Kinouchi K, Shinohara G, Kagawa H, Hashimoto K: Myocardial cyclic AMP augmentation with high-dose PDEIII inhibitor in terminal warm blood cardioplegia. Ann Thorac Cardiovasc Surg. 2009 Oct;15(5):311-7. [PubMed:19901885 ]
  4. Kucuk C, Akcan A, Akyyldyz H, Akgun H, Muhtaroglu S, Sozuer E: Effects of amrinone in an experimental model of hepatic ischemia-reperfusion injury. J Surg Res. 2009 Jan;151(1):74-9. doi: 10.1016/j.jss.2008.02.008. Epub 2008 Mar 13. [PubMed:18468627 ]
4. cAMP-specific 3',5'-cyclic phosphodiesterase 3
Kind
Protein
Organism
Human
Pharmacological action
unknown
References
  1. Weishaar RE, Kobylarz-Singer DC, Steffen RP, Kaplan HR: Subclasses of cyclic AMP-specific phosphodiesterase in left ventricular muscle and their involvement in regulating myocardial contractility. Circ Res. 1987 Oct;61(4):539-47. [PubMed:2820608 ]
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Drug created on July 24, 2007 06:34 / Updated on August 17, 2016 12:23