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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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Tocainida [INN-Spanish]
  • Tocainidum [INN-Latin]
Brand names
  • Tonocard
Brand name mixtures Not Available
Categories
  • Sodium channel blockers
  • Anti-Arrhythmia Agents
CAS number 41708-72-9
Weight Average: 192.2575
Monoisotopic: 192.126263144
Chemical Formula C11H16N2O
InChI Key InChIKey=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)
Plain Text
IUPAC Name
2-amino-N-(2,6-dimethylphenyl)propanamide
SMILES
CC(N)C(=O)NC1=C(C)C=CC=C1C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Acetanilides
Substructures
  • Amino Ketones
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Acetanilides
  • Carboxylic Acids and Derivatives
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Anilines
Pharmacology
Indication For the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that, in the judgment of the physician, are life-threatening.
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.
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
Pathway Name SMPDB ID
Smp00330 Tocainide Pathway SMP00330
Pharmacoeconomics
Manufacturers
  • Astrazeneca pharmaceuticals lp
Packagers Not Available
Dosage forms
Form Route Strength
Tablet Oral
Prices Not Available
Patents Not Available
Properties
State solid
Melting point 246-266 oC
Experimental Properties
Property Value Source
water solubility 1.07E+004 mg/L PhysProp
logP 1.1 PhysProp
Predicted Properties
Property Value Source
water solubility 1.60e+00 g/l ALOGPS
logP 0.55 ALOGPS
logP 0.58 ChemAxon Molconvert
logS -2.08 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 55.12 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 58.86 ChemAxon Molconvert
polarizability 21.59 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D06172 Link_out
KEGG Compound C07142 Link_out
PubChem Compound 38945 Link_out
PubChem Substance 46505385 Link_out
ChemSpider 35632 Link_out
BindingDB 50092595 Link_out
ChEBI 9611 Link_out
ChEMBL 9611 Link_out
Therapeutic Targets Database DAP000517 Link_out
PharmGKB PA451706 Link_out
Drug Product Database 598941 Link_out
RxList http://www.rxlist.com/cgi/generic3/tocainide.htm Link_out
Drugs.com http://www.drugs.com/mtm/tocainide.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/ton1451.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Tocainide Link_out
ATC Codes
  • C01BB03
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Sodium channel protein type 5 subunit alpha

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: Q14524 Link_out
Gene: SCN5A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Enzymes

1. Cytochrome P450 1A2

Actions: inhibitor

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 N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
Carriers

1. Serum albumin

Actions: other/unknown

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

UniProt ID: P02768 Link_out
Gene: ALB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2010 Mar 7. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:08

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.