41708-72-9

Tonocard,Astra,UK,1981

Tocainide is used for suppressing symptoms of ventricular arrhythmia and tachycardia, and for premature cardiac contractions.

ChEBI: A monocarboxylic acid amide in which 2,6-dimethylphenylaniline and isobutyric acid have combined to form the amide bond; used as a local anaesthetic.

The compound 2-amino-2',6'-propionoxylidide was synthesized by saturating with gaseous ammonia at room temperature a suspension of 50 g (0.195 mol) of 2-bromo-2',6'-propionoxylidide in a mixture of 500 ml of 95% alcohol and 400 ml of concentrated aqueous ammonia. The saturation was carried out under mechanical stirring. After 25 hours the mixture was resaturated with ammonia gas. The stirring at room temperature was continued for a total period of 116 hours, and a sample was taken at that time. Gas chromatographic analysis indicated that about 95% of the bromo compound had been converted to the desired product.
The solvents were evaporated in vacuo, and the residue was taken up in 80 ml of 3 M hydrochloric acid. After addition of 220 ml of water, the insoluble material was filtered off, washed with 100 ml of water and then dried. The insoluble material weighed 9.5 g and was mainly unreacted bromo compound. The filtrate was reacted with 50 ml of 7 M NaOH, extracted three times with methylene chloride (50 ml + 2 x 25 ml portions), dried over potassium carbonate, and then evaporated. The yield of residue was 26.8 g which corresponds to 71.4% of the theoretical yield. This residue was a colorless solidifying oil and was dissolved in 200 ml chloroform. Hydrogen chloride was bubbled in until a sample of the solution tested acidic to wet pH indicator paper. A precipitate was obtained and recovered by filtration. The precipitate was washed with chloroform and dried. The melting point was determined to be from 246°C to 247.5°C.

Apx;Citocard;Taquidil;Tonocard;Toquidil;Xylotocan.

Antiarrhythmic

Tocainide, an antidysrhythmic agent, was introduced in 1981 for the treatment of ventricular dysrhythmias. By 1984 its use was associated with cases of agranulocytosis, aplastic anaemia and thrombocytopenia, some of which were fatal. This led some regulatory authorities to restrict the indications for its use. The major manufacturer has subsequently restricted its use on a worldwide basis to the treatment of symptomatic ventricular dysrhythmias not responding to other therapy, or when other therapy is contraindicated.

The α-methyl group is believed to slow the rate of metabolism and, thereby, to contribute to oral activity. The plasma half-life of tocainide is approximately 12 hours, and nearly 50% of the drug may be excreted unchanged in the urine. Adverse effects associated with tocainide are like those observed with lidocaine—specifically, gastrointestinal disturbances and central nervous system effects.

Tocainide (Tonocard) is an orally effective antiarrhythmic agent with close structural similarities to lidocaine. Tocainide is indicated for the treatment of symptomatic ventricular arrhythmias refractory to more conventional therapy. Serious noncardiac adverse effects limit its use to patients with life-threatening arrhythmias.

Light-headedness, dizziness, or nausea occurs in approximately 15% of patients, paresthesias and numbness in 9%, and tremor in 8%.These adverse effects are generally mild in intensity, transient, and dose related. Overall, however, approximately 20% of patients prescribed tocainide discontinue therapy because of such effects. Serious immune-based side effects, such as pulmonary fibrosis, have been reported, and blood dyscrasias, such as agranulocytosis and thrombocytopenia, may occur in up to 0.2% of patients.

Tocainide, 2-amino-2,6-dimethylpropionanilide (18.1.8), is synthesized by reacting 2,6-dimethylaniline with 2-bromopropionic acid bromide and subsequent substitution of the bromine atom in the resulting amide (18.1.7) with an amino group.

When used with other class IB antiarrhythmic drugs, tocainide toxicity may be increased without significant gain in antiarrhythmic efficacy.

Patients who are hypersensitive to tocainide or to local anesthetics of the amide type should not be exposed to tocainide.The presence of second- or third-degree heart block in the absence of an artificial pacemaker also contraindicates the use of tocainide.