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Details

Stereochemistry RACEMIC
Molecular Formula C11H16N2O
Molecular Weight 192.258
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TOCAINIDE

SMILES

Cc1cccc(C)c1N=C(C(C)N)O

InChI

InChIKey=BUJAGSGYPOAWEI-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Description
Curator's Comment:: description was created based on several sources, including https://www.drugbank.ca/drugs/DB01056 | https://www.ncbi.nlm.nih.gov/pubmed/2499645 | https://www.ncbi.nlm.nih.gov/pubmed/3107988 | https://www.ncbi.nlm.nih.gov/pubmed/2108835 | https://www.ncbi.nlm.nih.gov/pubmed/3161487

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. The recommended initial dosage is 400 mg every 8 hours. The usual adult dosage is between 1200 and 1800 mg/day in a three-dose daily divided regimen. Doses beyond 2400 mg per day have been administered infrequently. Patients who tolerate the t.i.d. the regimen may be tried on a twice-daily regimen with careful monitoring. Tocainide commonly produces minor, transient, nervous system and gastrointestinal adverse reactions, but is otherwise generally well tolerated.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
TONOCARD

Approved Use

Unknown

Launch Date

4.68806402E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.2 μg/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TOCAINIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
7.8 μg × h/mL
200 mg single, intravenous
dose: 200 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
R(-)-TOCAINIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
11.7 μg × h/mL
200 mg single, intravenous
dose: 200 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
(S)-TOCAINIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
84 μg × h/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TOCAINIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
11.7 h
200 mg single, intravenous
dose: 200 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
R(-)-TOCAINIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
17.1 h
200 mg single, intravenous
dose: 200 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
(S)-TOCAINIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
15 h
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TOCAINIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
250 mg 2 times / day single, intravenous (starting)
Dose: 250 mg, 2 times / day
Route: intravenous
Route: single
Dose: 250 mg, 2 times / day
Sources:
unhealthy, 34 - 75 years
n = 50
Health Status: unhealthy
Condition: Acute Ventricular Arrhythmias
Age Group: 34 - 75 years
Sex: M+F
Population Size: 50
Sources:
Disc. AE: Hypotension...
Other AEs: Nausea, Vomiting...
AEs leading to
discontinuation/dose reduction:
Hypotension (3 patients)
Other AEs:
Nausea (1 patient)
Vomiting (1 patient)
Junctional rhythm (1 patient)
Sources:
600 mg 2 times / day multiple, oral
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 59 years (range: 28-83 years)
n = 67
Health Status: unhealthy
Condition: benign and potentially lethal ventricular arrhythmias
Age Group: 59 years (range: 28-83 years)
Sex: M+F
Population Size: 67
Sources:
Disc. AE: Ataxia, Tremor...
AEs leading to
discontinuation/dose reduction:
Ataxia (8 patients)
Tremor (8 patients)
Dizzy (8 patients)
Rash (4 patients)
Diarrhea (1 patient)
Nausea (1 patient)
Vomiting (1 patient)
Anorexia (1 patient)
Congestive heart failure (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Junctional rhythm 1 patient
250 mg 2 times / day single, intravenous (starting)
Dose: 250 mg, 2 times / day
Route: intravenous
Route: single
Dose: 250 mg, 2 times / day
Sources:
unhealthy, 34 - 75 years
n = 50
Health Status: unhealthy
Condition: Acute Ventricular Arrhythmias
Age Group: 34 - 75 years
Sex: M+F
Population Size: 50
Sources:
Nausea 1 patient
250 mg 2 times / day single, intravenous (starting)
Dose: 250 mg, 2 times / day
Route: intravenous
Route: single
Dose: 250 mg, 2 times / day
Sources:
unhealthy, 34 - 75 years
n = 50
Health Status: unhealthy
Condition: Acute Ventricular Arrhythmias
Age Group: 34 - 75 years
Sex: M+F
Population Size: 50
Sources:
Vomiting 1 patient
250 mg 2 times / day single, intravenous (starting)
Dose: 250 mg, 2 times / day
Route: intravenous
Route: single
Dose: 250 mg, 2 times / day
Sources:
unhealthy, 34 - 75 years
n = 50
Health Status: unhealthy
Condition: Acute Ventricular Arrhythmias
Age Group: 34 - 75 years
Sex: M+F
Population Size: 50
Sources:
Hypotension 3 patients
Disc. AE
250 mg 2 times / day single, intravenous (starting)
Dose: 250 mg, 2 times / day
Route: intravenous
Route: single
Dose: 250 mg, 2 times / day
Sources:
unhealthy, 34 - 75 years
n = 50
Health Status: unhealthy
Condition: Acute Ventricular Arrhythmias
Age Group: 34 - 75 years
Sex: M+F
Population Size: 50
Sources:
Anorexia 1 patient
Disc. AE
600 mg 2 times / day multiple, oral
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 59 years (range: 28-83 years)
n = 67
Health Status: unhealthy
Condition: benign and potentially lethal ventricular arrhythmias
Age Group: 59 years (range: 28-83 years)
Sex: M+F
Population Size: 67
Sources:
Congestive heart failure 1 patient
Disc. AE
600 mg 2 times / day multiple, oral
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 59 years (range: 28-83 years)
n = 67
Health Status: unhealthy
Condition: benign and potentially lethal ventricular arrhythmias
Age Group: 59 years (range: 28-83 years)
Sex: M+F
Population Size: 67
Sources:
Diarrhea 1 patient
Disc. AE
600 mg 2 times / day multiple, oral
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 59 years (range: 28-83 years)
n = 67
Health Status: unhealthy
Condition: benign and potentially lethal ventricular arrhythmias
Age Group: 59 years (range: 28-83 years)
Sex: M+F
Population Size: 67
Sources:
Nausea 1 patient
Disc. AE
600 mg 2 times / day multiple, oral
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 59 years (range: 28-83 years)
n = 67
Health Status: unhealthy
Condition: benign and potentially lethal ventricular arrhythmias
Age Group: 59 years (range: 28-83 years)
Sex: M+F
Population Size: 67
Sources:
Vomiting 1 patient
Disc. AE
600 mg 2 times / day multiple, oral
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 59 years (range: 28-83 years)
n = 67
Health Status: unhealthy
Condition: benign and potentially lethal ventricular arrhythmias
Age Group: 59 years (range: 28-83 years)
Sex: M+F
Population Size: 67
Sources:
Rash 4 patients
Disc. AE
600 mg 2 times / day multiple, oral
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 59 years (range: 28-83 years)
n = 67
Health Status: unhealthy
Condition: benign and potentially lethal ventricular arrhythmias
Age Group: 59 years (range: 28-83 years)
Sex: M+F
Population Size: 67
Sources:
Ataxia 8 patients
Disc. AE
600 mg 2 times / day multiple, oral
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 59 years (range: 28-83 years)
n = 67
Health Status: unhealthy
Condition: benign and potentially lethal ventricular arrhythmias
Age Group: 59 years (range: 28-83 years)
Sex: M+F
Population Size: 67
Sources:
Dizzy 8 patients
Disc. AE
600 mg 2 times / day multiple, oral
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 59 years (range: 28-83 years)
n = 67
Health Status: unhealthy
Condition: benign and potentially lethal ventricular arrhythmias
Age Group: 59 years (range: 28-83 years)
Sex: M+F
Population Size: 67
Sources:
Tremor 8 patients
Disc. AE
600 mg 2 times / day multiple, oral
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 59 years (range: 28-83 years)
n = 67
Health Status: unhealthy
Condition: benign and potentially lethal ventricular arrhythmias
Age Group: 59 years (range: 28-83 years)
Sex: M+F
Population Size: 67
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [Inhibition 2000 uM]
yes [Ki 12400 uM]
PubMed

PubMed

TitleDatePubMed
Open clinical studies at a referral center: chronic maintenance tocainide therapy in patients with recurrent sustained ventricular tachycardia refractory to conventional antiarrhythmic agents.
1980 Dec
Tocainide-induced ventricular fibrillation.
1981 Apr
New drugs for treating cardiac arrhythmias.
1981 Jan
Severe paranoia with concomitant tocainide and propranolol therapy.
1982 Mar-Apr
Nodal bradycardia induced by tocainide.
1983 Apr
Antiarrhythmic effects of tocainide and lidocaine in dogs.
1983 Aug
Tocainide. A review of its pharmacological properties and therapeutic efficacy.
1983 Aug
Paranoid psychosis induced by tocainide.
1984 Feb 25
Heart failure and hepatitis in a patient taking tocainide.
1984 Jan
Paranoid psychoses induced by tocainide.
1984 Mar 31
Facilitation of ventricular tachyarrhythmia induction by isoproterenol.
1984 Oct 1
[Analysis and toxicity of the anti-arrhythmia agent tocainide].
1985
A sequential double blind cross-over trial of tocainide hydrochloride in tinnitus.
1985 Apr
Confusion and paranoia associated with oral tocainide.
1985 Jan
Exacerbation of ventricular tachycardia by tocainide.
1985 Jan
Efficacy and safety of oral tocainide in refractory ventricular arrhythmia: a preliminary report on an open label study.
1986 Apr
Tocainide-induced granulomatous hepatitis.
1986 Jun 27
Successful treatment with tocainide of recessive generalized congenital myotonia.
1986 May
Effect on the seizure threshold in dogs of tocainide/lidocaine administration.
1987 Jul
Tocainide-induced reversible agranulocytosis and anemia.
1987 Mar
Congestive heart failure induced by six of the newer antiarrhythmic drugs.
1989 Nov 1
Pulmonary fibrosis associated with tocainide: report of a case with literature review.
1990 Feb
Effect of acidity on the enantiomeric resolution of thyroxine and tocainide by HPLC on a (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid column.
2002 Dec 31
A comparison of the antinociceptive effects of voltage-activated Na+ channel blockers in two rat models of neuropathic pain.
2003 Jan 5
Enantiomeric separation of tocainide and its analogues on an optically active crown ether-based stationary phase by liquid chromatography.
2003 May 9
Optimal requirements for high affinity and use-dependent block of skeletal muscle sodium channel by N-benzyl analogs of tocainide-like compounds.
2003 Oct
High-speed chiral separations on a microchip with UV detection.
2003 Sep
[Pharmacological treatment of trigeminal neuralgia: systematic review and metanalysis.].
2004 Dec
New potent mexiletine and tocainide analogues evaluated in vivo and in vitro as antimyotonic agents on the myotonic ADR mouse.
2004 Jul
Synthesis, structure and pharmacology of acyl-2,6-xylidines.
2004 May-Jun
Chiral separations on multichannel microfluidic chips.
2005 Dec
Ventricular tachycardia induced by biventricular pacing in patient with severe ischemic cardiomyopathy.
2005 Jun
Systemic administration of local anesthetic agents to relieve neuropathic pain.
2005 Oct 19
Robust randomised control trials needed for drug treatments for trigeminal neuralgia.
2006
Non-antiepileptic drugs for trigeminal neuralgia.
2006 Jul 19
Quantitative structure-pharmacokinetic relationships for drug clearance by using statistical learning methods.
2006 Mar
Synthesis and biological evaluation of chiral alpha-aminoanilides with central antinociceptive activity.
2007 Apr 19
[Eulenburg's paramyotonia congenita].
2007 Nov
Drug therapy considerations in arrhythmias in children.
2008 Aug 1
Cyclic metabolites: chemical and biological considerations.
2008 Feb
Preparation of two new liquid chromatographic chiral stationary phases based on diastereomeric chiral crown ethers incorporating two different chiral units and their applications.
2008 May 16
Constrained analogues of tocainide as potent skeletal muscle sodium channel blockers towards the development of antimyotonic agents.
2008 Nov
Liquid chromatographic direct resolution of tocainide and its analogs on a (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6-based chiral stationary phase containing residual silanol protecting n-octyl groups.
2009 Jan
Tinnitus: characteristics, causes, mechanisms, and treatments.
2009 Mar
Effects of a new potent analog of tocainide on hNav1.7 sodium channels and in vivo neuropathic pain models.
2010 Aug 25
Sodium channelopathies of skeletal muscle result from gain or loss of function.
2010 Jul
Update on methodologies available for ciguatoxin determination: perspectives to confront the onset of ciguatera fish poisoning in Europe.
2010 Jun 14
Tocainide analogues binding to human serum albumin: a HPLAC and circular dichroism study.
2010 Oct 10
Patents

Sample Use Guides

In Vivo Use Guide
Initial dose: 400 mg orally every 8 hours. Maintenance dose: 1200-1800 mg/day in 3 divided doses.
Route of Administration: Oral
In Vitro Use Guide
Cardiac myocytes were isolated from adult male Sprague-Dawley rats. Myocytes (6 x 10^5) in 50 mkl of incubation buffer were incubated with 1.3 mkM sea anemone toxin II, 13 nM [3H] BTXB (50 Ci/mmol), and 0.13 mM tetrodotoxin for 45-60 mm at 37C. Tetrodotoxin was added to prevent depolarization induced by sodium influx; without tetrodotoxin, no specific binding is observed. Various concentrations of tocainide enantiomers were included in the incubations. Assays were done in parallel with tubes containing 0.2 mM aconitine to define nonspecific binding. Concentration-response curves for both stereoisomers were performed on common preparations of cells and toxins. Reactions were terminated by adding 10 ml of KHS buffer (Krebs-Henseleit-BSA; 127 mM NaCl, 2.33 mM KC1, 1.30 mM KH2PO4, 1.23 mM MgSO4, 25 mM NaHCO3, 10 mM glucose, 50 mkM CaCl2, 1% BSA) equilibrated with 95% 02/5% CO2 and incubated at 3C for 1 min, then filtered through a Whatman GF-C 24-mm filter and washed five times with 5 ml of rinse buffer (25 mM Tris-Cl, pH 7.4, 130 mM NaCl, 5.5 mM KC1, 0.8 mM MgSO4, 5.5 mM glucose, 50 mkM CaCl2.) The filters were then dried and counted in Econofluor scintillation fluid. The retained radioactivity represents [3H]BTXB bound to the myocyte.
Name Type Language
TOCAINIDE
INN   MART.   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
TOCAINIDE [WHO-DD]
Common Name English
W-36095
Code English
TOCAINIDE [MI]
Common Name English
TOCAINIDE [VANDF]
Common Name English
TOCAINIDE [MART.]
Common Name English
TOCAINIDE [USAN]
Common Name English
TOCAINIDE [INN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C47793
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
NCI_THESAURUS C93038
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
WHO-ATC C01BB03
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
WHO-VATC QC01BB03
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
Code System Code Type Description
RXCUI
42359
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
PRIMARY RxNorm
LACTMED
Tocainide
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
PRIMARY
IUPHAR
7309
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
PRIMARY
PUBCHEM
38945
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
PRIMARY
NCI_THESAURUS
C66607
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
PRIMARY
MERCK INDEX
M10918
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
PRIMARY Merck Index
DRUG BANK
DB01056
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
PRIMARY
WIKIPEDIA
TOCAINIDE
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
PRIMARY
EVMPD
SUB11136MIG
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
PRIMARY
EPA CompTox
41708-72-9
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
PRIMARY
MESH
D016677
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
PRIMARY
ECHA (EC/EINECS)
255-505-0
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
PRIMARY
FDA UNII
27DXO59SAN
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
PRIMARY
INN
4056
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
PRIMARY
ChEMBL
CHEMBL1762
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
PRIMARY
CAS
41708-72-9
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
PRIMARY
DRUG CENTRAL
2686
Created by admin on Sat Jun 26 15:22:43 UTC 2021 , Edited by admin on Sat Jun 26 15:22:43 UTC 2021
PRIMARY