Disease relevance of Mexiletine

• This study examined the effectiveness of imipramine, mexiletine, pirmenol, procainamide, propafenone, quinidine, and sotalol in patients with ventricular tachyarrhythmias who were enrolled in the Electrophysiologic Study versus Electrocardiographic Monitoring trial [1].
• Mexiletine. Use in control of chronic drug-resistant ventricular arrhythmia [2].
• Mexiletine after myocardial infarction [3].
• Mexiletine for treatment of chronic painful diabetic neuropathy [4].
• Mexiletine has the advantage of less frequent administration and lower toxicity [5].

Psychiatry related information on Mexiletine

• Mexiletine in treatment-resistant bipolar disorder [6].

High impact information on Mexiletine

• The results provide insights for the selective suppression of the mutant phenotype by very low concentrations of drug and indicate that mexiletine equally suppresses the defect in all three known LQT3 mutants [7].
• Finally, treatment with mexiletine altered only sodium channel number; the Kd for [3H]BTXB and the IC50 for mexiletine were not different for myocytes prepared from control and mexiletine-treated rats [8].
• The administration of mexiletine to rats induced a dose-dependent increase in [3H]BTXB total specific binding (Bmax) on isolated cardiac myocytes [8].
• In this report we show that in vivo administration of the class I antiarrhythmic drug mexiletine to rats induces sodium channel upregulation in isolated cardiac myocytes [8].
• Mexiletine treatment had no effect on tendon reflexes, vibration threshold levels, beat-to-beat variation in heart rate during deep breathing, and postural blood pressure response [4].

Chemical compound and disease context of Mexiletine

• Safe treatment of resistant ventricular arrhythmias with a combination of amiodarone and quinidine or mexiletine [9].
• Combination of disopyramide and mexiletine for better tolerance and additive effects for treatment of ventricular arrhythmias [10].
• The ability of mexiletine monotherapy, quinidine monotherapy and mexiletine-quinidine combination therapy to suppress inducible sustained ventricular tachycardia was related to drug-induced changes in ventricular refractoriness, conduction times and monophasic action potential duration recorded from both ventricles [11].
• Thus, this study was designed to investigate a combination of mexiletine and propafenone in patients with refractory ventricular tachycardia [12].
• The arrhythmogenic and electrophysiologic properties of sotalol, a class III antiarrhythmic drug, administered alone and in combination with mexiletine, a class I antiarrhythmic drug, were compared in conscious dogs predisposed to torsade de pointes arrhythmias [13].

Biological context of Mexiletine

• Pharmacokinetics and nondialyzability of mexiletine in renal failure [14].
• Single-dose kinetics of mexiletine (MEX) was studied in six healthy subjects after three different formulations [15].
• Kinetics and bioavailability of mexiletine in healthy subjects [15].
• Thus, rbF1764/rhF1762 is a critical determinant of affinity and tissue-specific differences in mexiletine block of brain and heart sodium channels, but its role in drug interaction differs in these two channel isoforms [16].
• Two hours after mexiletine, mean cardiac and stroke work indexes decreased by 15% and 25%, respectively (both P less than 0.001), while heart rate and systemic vascular resistance increased by 10% and 20%, respectively (both P less than 0.05) [17].

Anatomical context of Mexiletine

• The subsequent efflux of lidocaine from the myocardium was more rapid that that of mexiletine in both paced and nonpaced groups [18].
• Molecular determinants of mexiletine structure for potent and use-dependent block of skeletal muscle sodium channels [19].
• In isolated cat papillary muscles, SC-40230 had a weak negative inotropic effect (IC20 = 3.3 X 10(-5) mol.litre-1) which was less than that previously reported for disopyramide phosphate (IC20 = 1.8 X 10(-5) mol.litre-1) or mexiletine (IC20 = 2.1 X 10(-5) mol.litre-1) [20].
• The electrophysiological effects of varying concentrations of mexiletine on isolated rabbit sinus node and atrial preparations [21].
• Effect of mexiletine on monophasic action potentials recorded from the right ventricle in man [22].

Associations of Mexiletine with other chemical compounds

• To answer this question, we determined the level of mRNA encoding cardiac Na+ channels and the number of the Na+ channels per cell in cultured neonatal rat cardiac myocytes after supplementation of the cells with the n - 3 PUFA eicosapentaenoic acid (EPA), the class I drug mexiletine, or both EPA and mexiletine for 3-4 days [23].
• 1. The ratios of affinities [IC50 of (+)-isomer/IC50 of (-)-isomer] were, for the C1 pairs: quinidine, 0.29; cinchonidine, 0.55; disopyramide, 1.11; RAC 109, 5.33; and for C2 pairs: flecainide, 1.03; mexiletine, 2.15; tocainide, 3.01 [24].
• A strong displacing effect of mexiletine on the binding of lidocaine to phosphatidylserine was observed in vitro [25].
• EMs, but not PMs, are susceptible to drug interactions between mexiletine and drugs that inhibit CYP2D6 (e.g. quinidine) [26].
• 2. In muscles driven at 0.02 Hz, neither mexiletine (10(-5) M) nor flecainide (10(-6) M) nor the combination of both drugs modified the action potential characteristics [27].

Gene context of Mexiletine

• Involvement of CYP1A2 in mexiletine metabolism [28].
• Mexiletine, a sodium channel blocker, is effective in shortening the QT interval corrected for heart rate (QTc) of patients with SCN5A mutations [29].
• Mexiletine shortened significantly the QT interval among LQT3 patients but not among LQT2 patients [30].
• High concentration (100 microM-1 mM) of mexiletine partially displaced the specific binding of [125I]cyanopindolol to human beta3-adrenoceptor [31].
• A class IB sodium channel blocker, mexiletine, is most effective in abbreviating QT interval in LQT3, but effectively reduces transmural dispersion of repolarization (TDR) and prevents the development of Torsade de Pointes (TdP) in all 3 models, suggesting its potential as an adjunctive therapy in LQT1 and LQT2 [32].

Analytical, diagnostic and therapeutic context of Mexiletine

• Continuous Holter ECG tapes were analyzed before, during, and after mexiletine [2].
• After cessation of treatment with mexiletine the number of sodium channels returned to normal within 12 d [8].
• Role of combination drug therapy with a class IC antiarrhythmic agent and mexiletine for ventricular tachycardia [33].
• The concentrations of mexiletine were measured with HPLC [34].
• Serial blood samples were drawn and analyzed for mexiletine concentration by gas chromatography [14].

References