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Identification
NameTocainide
Accession NumberDB01056  (APRD01266)
TypeSmall Molecule
GroupsApproved
Description

An antiarrhythmic agent which exerts a potential- and frequency-dependent block of sodium channels. [PubChem]

Structure
Thumb
Synonyms
2-Amino-2',6'-propionoxylidide
2-amino-N-(2,6-Dimethylphenyl)propanamide
2-Amino-N-(2,6-dimethylphenyl)propionamid
Alanyl-2,6-xylidide
Tocainida
Tocainidum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Tonocard Tab 400 mgtablet400 mgoralAstrazeneca Canada Inc1985-12-312003-07-24Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
TonocardNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Tocainide hydrochloride
ThumbNot applicableDBSALT001138
Categories
UNII27DXO59SAN
CAS number41708-72-9
WeightAverage: 192.2575
Monoisotopic: 192.126263144
Chemical FormulaC11H16N2O
InChI KeyInChIKey=BUJAGSGYPOAWEI-UHFFFAOYSA-N
InChI
InChI=1S/C11H16N2O/c1-7-5-4-6-8(2)10(7)13-11(14)9(3)12/h4-6,9H,12H2,1-3H3,(H,13,14)
IUPAC Name
2-amino-N-(2,6-dimethylphenyl)propanamide
SMILES
CC(N)C(=O)NC1=C(C)C=CC=C1C
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acid amides
Alternative Parents
Substituents
  • Alpha-amino acid amide
  • N-arylamide
  • Benzenoid
  • Monocyclic benzene moiety
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that, in the judgment of the physician, are life-threatening.
PharmacodynamicsTocainide is a primary amine analog of lidocaine with antiarrhythmic properties useful in the treatment of ventricular arrhythmias. Tocainide, like lidocaine, produces dose dependent decreases in sodium and potassium conductance, thereby decreasing the excitability of myocardial cells. In experimental animal models, the dose-related depression of sodium current is more pronounced in ischemic tissue than in normal tissue. Tocainide is a Class I antiarrhythmic compound with electrophysiologic properties in man similar to those of lidocaine, but dissimilar from quinidine, procainamide, and disopyramide.
Mechanism of actionTocainide acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. Tocainide binds preferentially to the inactive state of the sodium channels.The antiarrhythmic actions are mediated through effects on sodium channels in Purkinje fibers.
Related Articles
AbsorptionFollowing oral administration, the bioavailability approaches 100 percent, and is unaffected by food.
Volume of distributionNot Available
Protein bindingApproximately 10 percent bound to plasma protein.
Metabolism

Negligible first pass hepatic degradation. No active metabolites have been found.

Route of eliminationNot Available
Half lifeThe average plasma half-life in patients is approximately 15 hours. May be prolonged up to 35 hours in patients with severe renal function impairment (creatinine clearance less than 30 mL per min per 1.73 square meters of body surface area.
ClearanceNot Available
ToxicityThe oral LD50 of tocainide was calculated to be about 800 mg/kg in mice, 1000 mg/kg in rats, and 230 mg/kg in guinea pigs; deaths were usually preceded by convulsions.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Tocainide Action PathwayDrug actionSMP00330
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9157
Blood Brain Barrier+0.9154
Caco-2 permeable+0.7383
P-glycoprotein substrateNon-substrate0.6763
P-glycoprotein inhibitor INon-inhibitor0.9482
P-glycoprotein inhibitor IINon-inhibitor0.9932
Renal organic cation transporterNon-inhibitor0.962
CYP450 2C9 substrateNon-substrate0.8363
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6629
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5113
Ames testAMES toxic0.5064
CarcinogenicityNon-carcinogens0.5713
BiodegradationNot ready biodegradable0.9784
Rat acute toxicity2.4615 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9919
hERG inhibition (predictor II)Non-inhibitor0.9537
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tabletoral400 mg
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point246-266 °CPhysProp
water solubility1.07E+004 mg/LNot Available
logP0.76SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility1.6 mg/mLALOGPS
logP0.55ALOGPS
logP1.88ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)13.65ChemAxon
pKa (Strongest Basic)8.23ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area55.12 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity58.86 m3·mol-1ChemAxon
Polarizability21.59 Å3ChemAxon
Number of Rings1ChemAxon
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 ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesC01BB03
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Voltage-gated sodium channel activity involved in sa node cell action potential
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 respon...
Gene Name:
SCN5A
Uniprot ID:
Q14524
Molecular Weight:
226937.475 Da
References
  1. Georgijevic Milic L: [Molecular genetics in the hereditary form of long QT syndrome]. Med Pregl. 2000 Jan-Feb;53(1-2):51-4. [PubMed:10953551 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
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 ]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
no
Actions
other/unknown
General Function:
Toxic substance binding
Specific Function:
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
References
  1. Pistolozzi M, Franchini C, Corbo F, Muraglia M, De Giorgi M, Felix G, Bertucci C: Tocainide analogues binding to human serum albumin: a HPLAC and circular dichroism study. J Pharm Biomed Anal. 2010 Oct 10;53(2):179-85. doi: 10.1016/j.jpba.2010.03.005. Epub 2010 Mar 7. [PubMed:20359840 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23