Identification

Name
Tocainide
Accession Number
DB01056  (APRD01266)
Type
Small Molecule
Groups
Approved
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
Product Ingredients
IngredientUNIICASInChI Key
Tocainide hydrochloride2K7I38CKN571395-14-7AMZACPWEJDQXGW-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Tonocard Tab 400 mgTablet400 mgOralAstra Zeneca1985-12-312003-07-24Canada
International/Other Brands
Tonocard
Categories
UNII
27DXO59SAN
CAS number
41708-72-9
Weight
Average: 192.2575
Monoisotopic: 192.126263144
Chemical Formula
C11H16N2O
InChI Key
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

Pharmacology

Indication

For the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that, in the judgment of the physician, are life-threatening.

Structured Indications
Not Available
Pharmacodynamics

Tocainide 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 action

Tocainide 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.

TargetActionsOrganism
ASodium channel protein type 5 subunit alpha
inhibitor
Human
Absorption

Following oral administration, the bioavailability approaches 100 percent, and is unaffected by food.

Volume of distribution
Not Available
Protein binding

Approximately 10 percent bound to plasma protein.

Metabolism

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

Route of elimination
Not Available
Half life

The 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.

Clearance
Not Available
Toxicity

The 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
PathwayCategory
Tocainide Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB15189
KEGG Drug
D06172
KEGG Compound
C07142
PubChem Compound
38945
PubChem Substance
46505385
ChemSpider
35632
BindingDB
50092595
ChEBI
9611
ChEMBL
CHEMBL1762
Therapeutic Targets Database
DAP000517
PharmGKB
PA451706
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Tocainide
ATC Codes
C01BB03 — Tocainide

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral400 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)246-266 °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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

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/MSsplash10-00dl-0900000000-e3e09337d1b754b4c59c

Taxonomy

Description
This compound belongs to the class of organic compounds known as m-xylenes. These are aromatic compounds that contain a m-xylene moiety, which is a monocyclic benzene carrying exactly two methyl groups at the 1- and 3-positions.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Xylenes
Direct Parent
m-Xylenes
Alternative Parents
Propargyl-type 1,3-dipolar organic compounds / Carboximidic acids / Organopnictogen compounds / Organooxygen compounds / Monoalkylamines / Hydrocarbon derivatives
Substituents
M-xylene / Organic 1,3-dipolar compound / Propargyl-type 1,3-dipolar organic compound / Carboximidic acid derivative / Carboximidic acid / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound / Hydrocarbon derivative / Primary amine
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
monocarboxylic acid amide (CHEBI:9611)

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 pr...
Gene Name
SCN5A
Uniprot ID
Q14524
Uniprot Name
Sodium channel protein type 5 subunit alpha
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
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 colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
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]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:46