Mexiletine
- (RS ) -1 - (2,6- dimethylphenoxy ) -propan- 2-amine
- Rac-1 -(2,6- dimethylphenoxy ) -propan- 2-amine
- DL -1-( 2,6- dimethylphenoxy ) -propan- 2-amine
- (±) -1 - (2,6- dimethylphenoxy ) -propan- 2-amine
- 31828-71-4 (free base)
- 5370-01-4 ( mexiletine hydrochloride)
C01BB02
Antiarrhythmic agent of class Ib
Blockade of fast sodium channels
203-205 ° C ( mexiletine hydrochloride)
Water: 8.25 g · l-1 (25 ° C)
Attention
320 mg · kg -1 ( LD50, mouse, oral)
Template: Infobox chemical / molecular formula search available
Mexiletine is a drug against ventricular arrhythmia from the group of Ib antiarrhythmic drugs according to Vaughan- Williams. It is similar to the structure of lidocaine and tocainide. It was originally introduced as an appetite -reducing and anti-epileptic drug, until it was discovered its antiarrhythmic effects. The drug was marketed in Germany by Boehringer under the name Mexitil ®, but is not more since 1 September 2009 on the market.
Electrophysiological effects
Like all Class I antiarrhythmic agents mexiletine inhibits the fast sodium channel. It shortens the action potential of the heart chamber and stabilizes the membrane potential. Mexiletine does not prolong the QT interval and therefore offers itself as an alternative when a drug- induced ventricular tachycardia of torsade de pointes - type occurred or a long QT syndrome is, at the other antiarrhythmic drugs such as quinidine, sotalol, procainamide or disopyramide are contraindicated. Since the efficacy of mexiletine alone is quite modest, it is often administered with success in combination with quinidine, propranolol, procainamide, or amiodarone, with lower doses are required of the substances used in each case and thus the incidence of side effects may be reduced.
Hemodynamic effects and indications
Mexiletine has little effect on the contractile force of the heart or the circulatory system in patients with heart failure. Mexiletine is used to treat ventricular arrhythmias. A therapeutic trial is also useful when lidocaine has shown no efficacy. It is applicable to QT prolongation. A further indication is the treatment of myotonia.
Application
A slow increase in dosage in the early days is recommended until the desired effect has occurred on the arrhythmia or do not allow side-effects such as tremor further dose escalation. The maintenance dose is individually very different and should be discussed by mirrors provisions. In congenital deficiency of CYP2D6, kidney failure, severe liver disease or heart failure, the dose should be reduced.
Adverse effects
Side effects of mexiletine are dose-related and neurological nature. They include tremors, blurred vision, dizziness, mood swings and nausea. Rarely occurs thrombocytopenia. When sick sinus node syndrome is a risk of bradycardia or an extension of the sinus node recovery time ( SKEZ ). In new-onset bundle branch block, it should be discontinued. The function of the heart muscle is not inhibited by oral mexiletine, but this is supposed to happen for intravenous use.
Interactions
The substances phenytoin, phenobarbital, and rifampin fuel the metabolism of mexiletine in the liver and so weaken its effect. When you issue one of these agents with simultaneous administration of mexiletine so it can turn into a toxic dose, the effective dose, because now results in a lower degradation rate of mexiletine. Mexiletine can increase the efficacy of theophylline. Quinidine inhibits CYP2D6 and so slows down the rate of mexiletine. Antacids and atropine decrease the absorption in the intestine, metoclopramide increases.
Stereoisomerism
Mexiletine contains a stereocenter, and is therefore chiral. As a drug, the racemate is used, a 1:1 mixture of isomers ( R)-form and the ( S) form.