Flecainide

Common Name

Flecainide Description

A potent anti-arrhythmia agent, effective in a wide range of ventricliar and atrial arrhythmias and tachycardias. Paradoxically, however, in myocardial infarct patients with either symptomatic or asymptomatic arrhythmia, flecainide exacerbates the arrhythmia and is not recommended for use in these patients. [PubChem] Structure

Synonyms

Value Source (+-)-FlecainideChEBI CCRIS 313ChEBI FlecaineChEBI FlecainidaChEBI FlecainidumChEBI N-(2-Piperidinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamideChEBI ApocardMeSH Flecainide monoacetate, (S)-isomerMeSH Flecainide, 5-HO-N-(6-oxo)-derivativeMeSH Merck dura brand OF flecainide acetateMeSH Alpharma brand OF flecainide acetateMeSH Flecainide, 5-HO-N-(6-oxo)-derivative, (+-)-isomerMeSH FlecatabMeSH TambocorMeSH 3m Brand OF flecainide acetateMeSH Alphapharm brand OF flecainide acetateMeSH FlecaduraMeSH Flecainid-isisMeSH Flecainide acetateMeSH Flecainide monoacetate, (R)-isomerMeSH Flecainide, (R)-isomerMeSH Flecainide, (S)-isomerMeSH FlécaïneMeSH Riker brand OF flecainide acetateMeSH Acetate, flecainideMeSH Flecainid isisMeSH Flecainide monoacetateMeSH Flecainide monoacetate, (+-)-isomerMeSH United drug brand OF flecainide acetateMeSH

Chemical Formlia

C₁₇H₂₀F₆N₂O₃ Average Molecliar Weight

414.3427 Monoisotopic Molecliar Weight

414.137811746 IUPAC Name

N-(piperidin-2-ylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide Traditional Name

flecainide CAS Registry Number

54143-55-4 SMILES

InChI Identifier

InChI Key

DJBNUMBKLMJRSA-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of organic compounds known as benzamides. These are organic compounds containing a carboxamido substituent attached to a benzene ring. Kingdom

Organic compounds Super Class

Benzenoids Class

Benzene and substituted derivatives Sub Class

Benzoic acids and derivatives Direct Parent

Benzamides Alternative Parents

Phenoxy compounds

Phenol ethers

Benzoyl derivatives

Alkyl aryl ethers

Piperidines

Secondary carboxylic acid amides

Amino acids and derivatives

Dialkylamines

Azacyclic compounds

Organopnictogen compounds

Organofluorides

Organic oxides

Hydrocarbon derivatives

Alkyl fluorides

Substituents

Benzamide

Phenoxy compound

Benzoyl

Phenol ether

Alkyl aryl ether

Piperidine

Amino acid or derivatives

Carboxamide group

Secondary carboxylic acid amide

Carboxylic acid derivative

Secondary aliphatic amine

Ether

Azacycle

Organoheterocyclic compound

Secondary amine

Organohalogen compound

Alkyl halide

Alkyl fluoride

Organic nitrogen compound

Hydrocarbon derivative

Organic oxide

Organopnictogen compound

Organofluoride

Organonitrogen compound

Organooxygen compound

Amine

Organic oxygen compound

Aromatic heteromonocyclic compound

Molecliar Framework

Aromatic heteromonocyclic compounds External Descriptors

piperidines (CHEBI:75984 )

organofluorine compound (CHEBI:75984 )

aromatic ether (CHEBI:75984 )

monocarboxylic acid amide (CHEBI:75984 )

Ontology Status

Expected but not Quantified Origin

Drug

Biofunction

Anti-Arrhythmia Agents

Antiarrhythmic Agents

Application

Pharmaceutical

Cellliar locations

Membrane

Physical Properties State

Solid Experimental Properties

Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility3.24e-02 g/LNot Available LogP4.6Not Available

Predicted Properties

Property Value Source Water Solubility0.032 mg/mLALOGPS logP2.98ALOGPS logP3.19ChemAxon logS-4.1ALOGPS pKa (Strongest Acidic)13.68ChemAxon pKa (Strongest Basic)9.62ChemAxon Physiological Charge1ChemAxon Hydrogen Acceptor Count4ChemAxon Hydrogen Donor Count2ChemAxon Polar Surface Area59.59 ŲChemAxon Rotatable Bond Count9ChemAxon Refractivity88.4 m³·mol^-1ChemAxon Polarizability35.92 ųChemAxon Number of Rings2ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

Spectra Spectra

Spectrum Type Description Splash Key LC-MS/MS

LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-00dl-0095000000-644485d209c90776a32dView in MoNA LC-MS/MS

LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-00di-0190000000-201f2152d161a1ff83e5View in MoNA LC-MS/MS

LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-00di-0790000000-928874c4b348381ad1b8View in MoNA LC-MS/MS

LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-0596-0940000000-ee7a94ba0d7bcfa2fe93View in MoNA LC-MS/MS

LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-052g-1910000000-a32ac2f605f11fbbc5e0View in MoNA LC-MS/MS

LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-0297-1900000000-f1c49d25a6b161ff44d9View in MoNA LC-MS/MS

LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-014i-0000900000-9820e909cb01d45fa815View in MoNA LC-MS/MS

LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-00kb-2009500000-68b872fada8afdd4e580View in MoNA LC-MS/MS

LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-0f6t-5019000000-8fa5e4257c88beda0ea1View in MoNA LC-MS/MS

LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-0uea-8069000000-149a79cf429446ec77c2View in MoNA LC-MS/MS

LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-0uei-6292000000-103ccdef98c4b6c9e408View in MoNA LC-MS/MS

LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-0pdi-8970000000-9258d139b203d6c98df0View in MoNA Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available MS

Mass Spectrum (Electron Ionization)splash10-001i-9000000000-b732167df77d39193144View in MoNA

Biological Properties Cellliar Locations

Membrane

Biofluid Locations

Blood

Urine

Tissue Location

Not Available Pathways

Name SMPDB Link KEGG Link Flecainide PathwaySMP00331Not Available

Normal Concentrations

Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01195

21059682

details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01195

21059682

details

Abnormal Concentrations

Not Available Predicted Concentrations

Biofluid Value Original age Original sex Original condition Comments Blood0-2 uMAdlit (>18 years old)BothNormalPredicted based on drug qualities Blood0-1 umol/mmol creatinineAdlit (>18 years old)BothNormalPredicted based on drug qualities

Associated Disorders and Diseases Disease References

None Associated OMIM IDs

None External Links DrugBank ID

DB01195 DrugBank Metabolite ID

Not Available Phenol Explorer Compound ID

Not Available Phenol Explorer Metabolite ID

Not Available FoodDB ID

Not Available KNApSAcK ID

Not Available Chemspider ID

3239 KEGG Compound ID

C07001 BioCyc ID

Not Available BiGG ID

Not Available Wikipedia Link

Flecainide NuGOwiki Link

HMDB15326 Metagene Link

HMDB15326 METLIN ID

Not Available PubChem Compound

3356 PDB ID

Not Available ChEBI ID

127588

Product: Tubulysin A

References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References

1. Gill JS, Mehta D, Ward DE, Camm AJ: Efficacy of flecainide, sotalol, and verapamil in the treatment of right ventricular tachycardia in patients without overt cardiac abnormality. Br Heart J. 1992 Oct;68(4):392-7. [PubMed:1449923 ]
2. Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, Arensberg D, Baker A, Friedman L, Greene HL, et al.: Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med. 1991 Mar 21;324(12):781-8. [PubMed:1900101 ]
3. Sakurada H, Hiyoshi Y, Tejima T, Yanase O, Tokuyasu Y, Watanabe K, Motomiya T, Sugiura M, Hiraoka M: [Effects of oral flecainide treatment of refractory tachyarrhythmias]. Kokyu To Junkan. 1990 May;38(5):471-6. [PubMed:2115193 ]
4. Greenberg HM, Dwyer EM Jr, Hochman JS, Steinberg JS, Echt DS, Peters RW: Interaction of ischaemia and encainide/flecainide treatment: a proposed mechanism for the increased mortality in CAST I. Br Heart J. 1995 Dec;74(6):631-5. [PubMed:8541168 ]
5. Gasparini M, Priori SG, Mantica M, Napolitano C, Galimberti P, Ceriotti C, Simonini S: Flecainide test in Brugada syndrome: a reproducible but risky tool. Pacing Clin Electrophysiol. 2003 Jan;26(1 Pt 2):338-41. [PubMed:12687841 ]

Enzymes

General function:

Involved in monooxygenase activity

Specific function:

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.

Gene Name:

CYP2C9

Uniprot ID:

P11712

Molecular weight:

55627.365

References

1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

General function:

Involved in monooxygenase activity

Specific function:

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.

Gene Name:

CYP2D6

Uniprot ID:

P10635

Molecular weight:

55768.94

References

1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

General function:

Involved in ion channel activity

Specific function:

This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. This sodium channel may be present in both denervated and innervated skeletal muscle

Gene Name:

SCN4A

Uniprot ID:

P35499

Molecular weight:

208059.2

References

1. Desaphy JF, De Luca A, Didonna MP, George AL Jr, Camerino Conte D: Different flecainide sensitivity of hNav1.4 channels and myotonic mutants explained by state-dependent block. J Physiol. 2004 Jan 15;554(Pt 2):321-34. Epub 2003 Nov 7. [PubMed:14608015 ]

General function:

Involved in ion channel activity

Specific function:

This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential in the electrocardiogram

Gene Name:

SCN5A

Uniprot ID:

Q14524

Molecular weight:

226937.5

References

1. Nagatomo T, January CT, Makielski JC: Preferential block of late sodium current in the LQT3 DeltaKPQ mutant by the class I(C) antiarrhythmic flecainide. Mol Pharmacol. 2000 Jan;57(1):101-7. [PubMed:10617684 ]
2. Benhorin J, Taub R, Goldmit M, Kerem B, Kass RS, Windman I, Medina A: Effects of flecainide in patients with new SCN5A mutation: mutation-specific therapy for long-QT syndrome? Circulation. 2000 Apr 11;101(14):1698-706. [PubMed:10758053 ]
3. Priori SG, Napolitano C, Schwartz PJ, Bloise R, Crotti L, Ronchetti E: The elusive link between LQT3 and Brugada syndrome: the role of flecainide challenge. Circulation. 2000 Aug 29;102(9):945-7. [PubMed:10961955 ]
4. Cerrone M, Crotti L, Faggiano G, De Michelis V, Napolitano C, Schwartz PJ, Priori SG: [Long QT syndrome and Brugada syndrome: 2 aspects of the same disease?]. Ital Heart J Suppl. 2001 Mar;2(3):253-7. [PubMed:11307783 ]
5. Viswanathan PC, Bezzina CR, George AL Jr, Roden DM, Wilde AA, Balser JR: Gating-dependent mechanisms for flecainide action in SCN5A-linked arrhythmia syndromes. Circulation. 2001 Sep 4;104(10):1200-5. [PubMed:11535580 ]
6. Ramos E, Oleary ME: State-dependent trapping of flecainide in the cardiac sodium channel. J Physiol. 2004 Oct 1;560(Pt 1):37-49. Epub 2004 Jul 22. [PubMed:15272045 ]
7. Shimizu W, Antzelevitch C, Suyama K, Kurita T, Taguchi A, Aihara N, Takaki H, Sunagawa K, Kamakura S: Effect of sodium channel blockers on ST segment, QRS duration, and corrected QT interval in patients with Brugada syndrome. J Cardiovasc Electrophysiol. 2000 Dec;11(12):1320-9. [PubMed:11196553 ]
8. Liu H, Atkins J, Kass RS: Common molecular determinants of flecainide and lidocaine block of heart Na+ channels: evidence from experiments with neutral and quaternary flecainide analogues. J Gen Physiol. 2003 Mar;121(3):199-214. [PubMed:12601084 ]
9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

PMID: 11133067

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