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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
AmcoralNot AvailableNot Available
AmrinonaSpanishINN
AmrinonumLatinINN
InamrinoneNot AvailableUSAN
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
AmcoralNot Available
InocorNot Available
Brand mixturesNot Available
SaltsNot 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
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.
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 substrateInhibitor0.5328
CYP450 2D6 substrateNon-inhibitor0.9651
CYP450 2C19 substrateInhibitor0.8994
CYP450 3A4 substrateNon-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
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage formsNot Available
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
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
ATC CodesC01CE01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AmobarbitalBarbiturates may increase the metabolism of Calcium Channel Blockers.
AtracuriumMay enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing).
ButabarbitalBarbiturates may increase the metabolism of Calcium Channel Blockers.
ButalbitalBarbiturates may increase the metabolism of Calcium Channel Blockers.
Calcium AcetateCalcium Salts may diminish the therapeutic effect of Calcium Channel Blockers.
Calcium carbonateCalcium Salts may diminish the therapeutic effect of Calcium Channel Blockers.
Calcium ChlorideCalcium Salts may diminish the therapeutic effect of Calcium Channel Blockers.
CimetidineCimetidine may increase the serum concentration of Calcium Channel Blockers.
Cisatracurium BesylateMay enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing).
ClarithromycinMacrolide Antibiotics may decrease the metabolism of Calcium Channel Blockers.
ClopidogrelMay diminish the therapeutic effect of Clopidogrel. Exceptions: Clevidipine.
DoxazosinAlpha1-Blockers may enhance the hypotensive effect of Calcium Channel Blockers.
FluconazoleFluconazole may increase the serum concentration of Calcium Channel Blockers. Exceptions: Clevidipine.
FosphenytoinMay increase the serum concentration of Fosphenytoin.
ItraconazoleAntifungal Agents (Azole Derivatives, Systemic) may enhance the adverse/toxic effect of Calcium Channel Blockers. Specifically, itraconazole may enhance the negative inotropic effects of verapamil or diltiazem. Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Calcium Channel Blockers. Fluconazole and isavuconazonium likely exert weaker effects than other azoles and are addressed in separate monographs.
Magnesium oxideMay enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers.
Magnesium salicylateMay enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers.
MethohexitalBarbiturates may increase the metabolism of Calcium Channel Blockers.
NafcillinNafcillin may increase the metabolism of Calcium Channel Blockers. Exceptions: Clevidipine.
NitroprussideMay enhance the hypotensive effect of Nitroprusside.
PancuroniumMay enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing).
PentobarbitalBarbiturates may increase the metabolism of Calcium Channel Blockers.
PhenobarbitalBarbiturates may increase the metabolism of Calcium Channel Blockers.
PhenoxybenzamineAlpha1-Blockers may enhance the hypotensive effect of Calcium Channel Blockers.
PhentolamineAlpha1-Blockers may enhance the hypotensive effect of Calcium Channel Blockers.
PhenytoinMay increase the serum concentration of Phenytoin.
PosaconazoleAntifungal Agents (Azole Derivatives, Systemic) may enhance the adverse/toxic effect of Calcium Channel Blockers. Specifically, itraconazole may enhance the negative inotropic effects of verapamil or diltiazem. Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Calcium Channel Blockers. Fluconazole and isavuconazonium likely exert weaker effects than other azoles and are addressed in separate monographs.
PrazosinAlpha1-Blockers may enhance the hypotensive effect of Calcium Channel Blockers.
RifampicinRifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers.
RifapentineRifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers.
RocuroniumMay enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing).
SecobarbitalBarbiturates may increase the metabolism of Calcium Channel Blockers.
SilodosinAlpha1-Blockers may enhance the hypotensive effect of Calcium Channel Blockers.
SulfisoxazoleMacrolide Antibiotics may decrease the metabolism of Calcium Channel Blockers.
TamsulosinAlpha1-Blockers may enhance the hypotensive effect of Calcium Channel Blockers.
TelithromycinMacrolide Antibiotics may decrease the metabolism of Calcium Channel Blockers.
TerazosinAlpha1-Blockers may enhance the hypotensive effect of Calcium Channel Blockers.
VecuroniumMay enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing).
VoriconazoleAntifungal Agents (Azole Derivatives, Systemic) may enhance the adverse/toxic effect of Calcium Channel Blockers. Specifically, itraconazole may enhance the negative inotropic effects of verapamil or diltiazem. Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Calcium Channel Blockers. Fluconazole and isavuconazonium likely exert weaker effects than other azoles and are addressed in separate monographs.
Food InteractionsNot Available

Targets

1. 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

2. 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

3. 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

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

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Drug created on July 24, 2007 06:34 / Updated on March 28, 2014 09:52