You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameAmrinone
Accession NumberDB01427
Typesmall molecule
Groupsapproved
Description

Amrinone (or inamrinone) is a type 3 pyridine phosphodiesterase inhibitor. It is used in the treatment of congestive heart failure.

Structure
Thumb
Synonyms
SynonymLanguageCode
AmrinonaSpanishINN
AmrinonumLatinINN
InamrinoneNot AvailableUSAN
SaltsNot Available
Brand names
NameCompany
AmcoralNot Available
InocorNot Available
Brand mixturesNot Available
Categories
CAS number60719-84-8
WeightAverage: 187.198
Monoisotopic: 187.074561925
Chemical FormulaC10H9N3O
InChI KeyRNLQIBCLLYYYFJ-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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassPyridines and Derivatives
SubclassBipyridines and Oligopyridines
Direct parentBipyridines and Oligopyridines
Alternative parentsPyridinones; Dihydropyridines; Aminopyridines and Derivatives; Primary Aromatic Amines; Polyamines
Substituentsaminopyridine; dihydropyridine; pyridinone; hydropyridine; primary aromatic amine; polyamine; amine; primary amine; organonitrogen compound
Classification descriptionThis compound belongs to the bipyridines and oligopyridines. These are organic compounds containing two pyridine rings linked to each other.
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.
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
Property Value Probability
Human Intestinal Absorption + 0.9522
Blood Brain Barrier + 0.9525
Caco-2 permeable + 0.8867
P-glycoprotein substrate Non-substrate 0.6469
P-glycoprotein inhibitor I Non-inhibitor 0.9338
P-glycoprotein inhibitor II Non-inhibitor 0.9946
Renal organic cation transporter Non-inhibitor 0.9258
CYP450 2C9 substrate Non-substrate 0.8642
CYP450 2D6 substrate Non-substrate 0.8389
CYP450 3A4 substrate Non-substrate 0.6443
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Inhibitor 0.5328
CYP450 2D6 substrate Non-inhibitor 0.9651
CYP450 2C19 substrate Inhibitor 0.8994
CYP450 3A4 substrate Non-inhibitor 0.6534
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5933
Ames test Non AMES toxic 0.8492
Carcinogenicity Non-carcinogens 0.9116
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.9371 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9923
hERG inhibition (predictor II) Non-inhibitor 0.7418
Pharmacoeconomics
Manufacturers
  • Baxter healthcare corp anesthesia critical care
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • Sanofi aventis us llc
Packagers
Dosage forms
FormRouteStrength
LiquidIntravenous bolus
LiquidIntravenous drip
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 solubility5.60e+00 g/lALOGPS
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 area68.01ChemAxon
rotatable bond count1ChemAxon
refractivity53.89ChemAxon
polarizability18.94ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot 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 ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00231
KEGG CompoundC13594
PubChem Compound3698
PubChem Substance46504647
ChemSpider3570
BindingDB34651
Therapeutic Targets DatabaseDAP001392
PharmGKBPA164746803
WikipediaAmrinone
ATC CodesC01CE01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

Targets

1. cGMP-inhibited 3',5'-cyclic phosphodiesterase A

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
cGMP-inhibited 3',5'-cyclic phosphodiesterase A Q14432 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  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
  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
  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. Epub 2008 Mar 13. Pubmed

2. cAMP-specific 3',5'-cyclic phosphodiesterase 4B

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
cAMP-specific 3',5'-cyclic phosphodiesterase 4B Q07343 Details

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
  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

3. Tumor necrosis factor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Tumor necrosis factor P01375 Details

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
  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
  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
  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
  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

4. cAMP-specific 3',5'-cyclic phosphodiesterase 3

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details

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

Comments
comments powered by Disqus
Drug created on July 24, 2007 06:34 / Updated on March 28, 2014 09:52