Description
Mexiletine is effective both parenterally and
orally , . Because the substance has a
large distribution volume, a high initial dose is
necessary.
Originator
Mexitil,Boehringer Ingelheim,US,1976
Uses
Mexiletine is a useful analgesia.It is used in treatment of amyotrophic lateral sclerosis comprising administering a bile acid and a phenylbutyrate compound and an additional therapeutic agent.
Uses
Mexiletine is used for ventricular extrasystole and ventricular tachycardia, and ventricular
fibrillation (including during the severe period of myocardial infarction).
Uses
Cardiac depressant (anti-arrhythmic).
Definition
ChEBI: An aromatic ether which is 2,6-dimethylphenyl ether of 2-aminopropan-1-ol.
Manufacturing Process
The sodium salt of dimethyl phenol was reacted with chloroacetone and this
product with hydroxylamine to give the starting material.
245 g of this 1-(2',6'-dimethyl-phenoxy)-propanone-(2)-oxime were dissolved
in 1,300 cc of methanol, and the solution was hydrogenated at 5 atmospheres
gauge and 60°C in the presence of Raney nickel. After the calculated amount
of hydrogen had been absorbed, the catalyst was filtered off, the methanol
was distilled out of the filtrate,and the residue, raw 1-(2',6'-dimethylphenoxy)-2-amino-propane, was dissolved in ethanol. The resulting solution
was acidified with ethereal hydrochloric acid, the acidic solution was allowed
to cool, and the precipitate formed thereby was collected by vacuum filtration.
The filter cake was dissolved in ethanol and recystallized therefrom by
addition of ether. 140.5 g (51.5% of theory) of a substance having a melting
point of 203°C to 205°C were obtained, which was identified to be 1-(2',6'-
dimethyl-phenoxy)-2-anino-propane hydrochloride.
brand name
Mexitil (Boehringer Ingelheim).
Therapeutic Function
Antiarrhythmic
Clinical Use
Mexiletine (Mexitil) is an antiarrhythmic agent with
pharmacological and antiarrhythmic properties similar
to those of lidocaine and tocainide. Like tocainide,mexiletine
is available for oral administration.
Mexiletine is useful as an antiarrhythmic agent in the
management of patients with either acute or chronic
ventricular arrhythmias.While it is not at present an indication
for use, there is interest in using mexiletine to
treat the congenital long QT syndrome when an abnormality
in the SCN5A gene (LQTS 3) has been found.
Side effects
A very narrow therapeutic window limits mexiletine
use. The first signs of toxicity manifest as fine tremor of
the hands, followed by dizziness and blurred vision.
Hypotension, sinus bradycardia, and widening of the
QRS complex have been noted as the most common
unwanted cardiovascular effects of IV mexiletine. The
side effects of oral maintenance therapy include reversible
upper gastrointestinal distress, tremor, lightheadedness,
and coordination difficulties. These effects
generally are not serious and can be reduced by downward
dose adjustment or administering the drug with
meals. Cardiovascular adverse effects, which are less
common, include palpitations, chest pain, and angina or
anginalike pain.
Synthesis
Mexiletine is 1-methyl-2-(2,2-dimethylphenoxy)ethylamine (18.1.11).
Mexiletine is synthesized by reacting the sodium salt of 2,6-dimethylphenol with chloroacetone,
forming 1-(2,6-dimethylphenoxy)-2-propanone (18.1.9). Reacting this with hydroxylamine
gives the corresponding oxime (18.1.10). Reduction of the oximine group using
hydrogen over Raney nickel gives mexiletine (18.1.11).
Drug interactions
An upward adjustment in dose may be required when
mexiletine is administered with phenytoin or rifampin,
since these drugs stimulate the hepatic metabolism of
mexiletine, reducing its plasma concentration.
Precautions
Mexiletine is contraindicated in the presence of cardiogenic
shock or preexisting second- or third-degree heart
block in the absence of a cardiac pacemaker. Caution
must be exercised in administration of the drug to patients
with sinus node dysfunction or disturbances of intraventricular
conduction.
