Tocainide

Tocainide (Tonocard) is a class Ib antiarrhythmic agent. It is no longer sold in the United States.

Tocainide
Clinical data
AHFS/Drugs.comMicromedex Detailed Consumer Information
MedlinePlusa601248
ATC code
Pharmacokinetic data
Bioavailability0.9-1 (oral)
Protein binding10-20%
Metabolismglucuronidation (primary)
Elimination half-life9-14 R, 13-20 S
Excretion30-50% urine (unchanged)
Identifiers
IUPAC name
  • N-(2,6-dimethylphenyl)alaninamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.050.441
Chemical and physical data
FormulaC11H16N2O
Molar mass192.262 g·mol−1
3D model (JSmol)
SMILES
  • O=C(Nc1c(cccc1C)C)C(N)C
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) Y
  • Key:BUJAGSGYPOAWEI-UHFFFAOYSA-N Y
  (verify)

Pharmacokinetics

Tocainide is a lidocaine analog, that does not have significant 1st pass metabolism. It is found in two enantiomers. The R isomer is 4x as potent as the S. Oral bioavailability is 0.9-1.0. In the blood tocainide is 10-20% protein bound. The Volume of distribution is 2.5-3.5 L/kg. 30-50% is excreted unchanged in the urine. The more active R-isomer is cleared faster in anephric patients or those with severe renal dysfunction. The main metabolite is the glucuronidated tocainide carbamic acid. The glucuronosyl transferase is apparently induced by rifampin. Weak inhibition of Cyp1A2 leads to a mild theophylline interaction. (Not verbatim)

Synthesis
Tocainide synthesis:[1][2][3][4]

References
  1. DE 2235745, Boyes RN, Byrnes EW, "Antiarrhythmisch Wirksame Verbindung, Verfahren zu Deren Herstellung und Deren Verwendung", issued 1972, assigned to Astra Pharmaceutical Products Inc.
  2. GB 1461602, "Primary Amino Acylanilides Methods of Making the Same and Use as Antiarrhythmic Drugs", issued 1974, assigned to Astra Pharmaceutical Products Inc.
  3. DE 2400540, Boyes RN, Duce BR, Smith EM, Byrnes EW, "Primaeraminoacylanilide, Verfahren zu Deren Herstellung und Sie Enthaltende Arzneimittel", issued 1974, assigned to Astra Pharmaceutical Products Inc.
  4. Byrnes EW, McMaster PD, Smith ER, Blair MR, Boyes RN, Duce BR, et al. (October 1979). "New antiarrhythmic agents. 1. Primary alpha-amino anilides". Journal of Medicinal Chemistry. 22 (10): 1171–6. doi:10.1021/jm00196a005. PMID 513064.

Further reading
  • Burton ME (2006). Applied Pharmacokinetics & Pharmacodynamics: Principles of Therapeutic Drug Monitoring (4th ed.). Philadelphia: Lippincott Williams & Wilkins.



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