Identification

Name
Amrinone
Accession Number
DB01427
Type
Small Molecule
Groups
Approved
Description

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

Structure
Thumb
Synonyms
  • Amrinona
  • Amrinonum
  • Inamrinone
External IDs
C01CE01 / WIN 40680 / WIN-40680
Product Ingredients
IngredientUNIICASInChI Key
Amrinone lactateI229274Y5B75898-90-7DOSIONJFGDSKCQ-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Inocor Liq 5mg/mlLiquid5 mgIntravenousSanofi1984-12-312000-07-24Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
InamrinoneInjection5 mg/1mLIntravenousBedford Pharmaceuticals2000-07-012009-10-31Us
International/Other Brands
Amcoral / Inocor
Categories
UNII
JUT23379TN
CAS number
60719-84-8
Weight
Average: 187.198
Monoisotopic: 187.074561925
Chemical Formula
C10H9N3O
InChI Key
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

Pharmacology

Indication

Used in the treatment of congestive heart failure.

Pharmacodynamics

Amrinone 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 action

Amrinone 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.

TargetActionsOrganism
AcGMP-inhibited 3',5'-cyclic phosphodiesterase A
inhibitor
Human
UcAMP-specific 3',5'-cyclic phosphodiesterase 4B
inhibitor
Human
UTumor necrosis factor
inhibitor
Human
UcAMP-specific 3',5'-cyclic phosphodiesterase 3
inhibitor
Human
Absorption
Not Available
Volume of distribution
  • 1.2 L/kg [normal volunteers]
Protein binding

10 to 49%

Metabolism

Hepatic.

Route of elimination

The 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 life

5 to 8 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2-mercaptobenzothiazoleThe therapeutic efficacy of 2-mercaptobenzothiazole can be increased when used in combination with Amrinone.
AcepromazineThe risk or severity of hypotension can be increased when Acepromazine is combined with Amrinone.
AcetaminophenAcetaminophen may decrease the excretion rate of Amrinone which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Amrinone which could result in a higher serum level.
AlprazolamAlprazolam may decrease the excretion rate of Amrinone which could result in a higher serum level.
AmilorideAmiloride may increase the excretion rate of Amrinone which could result in a lower serum level and potentially a reduction in efficacy.
AmitriptylineAmrinone may decrease the excretion rate of Amitriptyline which could result in a higher serum level.
AmlodipineAmlodipine may decrease the excretion rate of Amrinone which could result in a higher serum level.
AmobarbitalThe metabolism of Amrinone can be increased when combined with Amobarbital.
AmorolfineThe therapeutic efficacy of Amorolfine can be increased when used in combination with Amrinone.
Food Interactions
Not 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 References
Not Available
External Links
Human Metabolome Database
HMDB0015496
KEGG Drug
D00231
KEGG Compound
C13594
PubChem Compound
3698
PubChem Substance
46504647
ChemSpider
3570
BindingDB
34651
ChEBI
2686
ChEMBL
CHEMBL12856
Therapeutic Targets Database
DAP001392
PharmGKB
PA164746803
Wikipedia
Amrinone
ATC Codes
C01CE01 — Amrinone

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Taylor Pharmaceuticals
Dosage forms
FormRouteStrength
InjectionIntravenous5 mg/1mL
LiquidIntravenous5 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)294-297Lesher,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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00lr-3900000000-f6b4ee8cb119f30be206

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Bipyridines and oligopyridines
Direct Parent
Bipyridines and oligopyridines
Alternative Parents
Pyridinones / Dihydropyridines / Aminopyridines and derivatives / Heteroaromatic compounds / Lactams / Azacyclic compounds / Primary amines / Organopnictogen compounds / Organooxygen compounds / Organic oxides
show 1 more
Substituents
Bipyridine / Aminopyridine / Dihydropyridine / Pyridinone / Hydropyridine / Heteroaromatic compound / Lactam / Azacycle / Amine / Primary amine
show 8 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

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
Uniprot Name
cGMP-inhibited 3',5'-cyclic phosphodiesterase A
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]
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 f...
Gene Name
PDE4B
Uniprot ID
Q07343
Uniprot Name
cAMP-specific 3',5'-cyclic phosphodiesterase 4B
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 ac...
Gene Name
TNF
Uniprot ID
P01375
Uniprot Name
Tumor necrosis factor
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]
4. cAMP-specific 3',5'-cyclic phosphodiesterase 3
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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]

Drug created on July 24, 2007 06:34 / Updated on August 02, 2018 07:51