Broad antiarrhythmic effect of mexiletine in different arrhythmia models

Frommeyer, Gerrit; Garthmann, Jonas; Ellermann, Christian; Dechering, Dirk G.; Kochhäuser, Simon; Reinke, Florian; Köbe, Julia; Wasmer, Kristina; Eckardt, Lars

doi:10.1093/europace/eux221

Cited by 24 publications

(30 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mexiletine also increased the atrial refractory period and hence inhibited AF. 16 In the current study, using hiPSC-CMs from an SQTS1 patient, we also detected the effective results of mexiletine, prolonging APD, and attenuating arrhythmic events. Although mexiletine inhibited I Kr in SQTS1 hiPSC-CMs, its effect is much smaller than that of quinidine, suggesting that the APD-prolonging effect might result from multiple effects in addition to the inhibition of I Kr .…”

Section: Discussionmentioning

confidence: 53%

“…Mexiletine, a sodium channel blocker, was also demonstrated to have potent antiarrhythmic properties in a model of SQTS or atrial fibrillation (AF). 16 In that study, nine isolated rabbit hearts were perfused with the K ATP channel opener pinacidil to simulate SQTS. Pinacidil shortened ventricular repolarization and enhanced induction of ventricular fibrillation (VF).…”

Section: Discussionmentioning

confidence: 99%

“…Mexiletine has been shown to have antiarrhythmic properties in an animal model of SQTS. 16 Therefore, we tested the APDprolonging effects of mexiletine at different concentrations (10, 30, and 100 μM) in SQTS1 hiPSC-CMs and found that 100 μM mexiletine prolonged APD90 significantly, from 250.0 ± 27.4 ms to 310.2 ± 32.6 ms (P < 0.05). In addition, 100 μM mexiletine reduced V max significantly (control, 34.2 ± 4.6 V/s; mexiletine, 23.9 ± 2.8 V/s) and APA (control, 136.7 ± 3.5 mV; mexiletine, 122.1 ± 4.9 mV).…”

Section: Mexiletinementioning

confidence: 99%

“…Ivabradine, mexiletine, and ranolazine have been shown to have antiarrhythmic effect in an animal model of SQTS. [16][17][18] Ajmaline has been shown to have multiple ion channel-blocking effects, including the KCNH2 channel. 19,20 However, these drugs have not been tested in SQTS patients.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Drug Testing in Human‐Induced Pluripotent Stem Cell–Derived Cardiomyocytes From a Patient With Short QT Syndrome Type 1

Zhao

El‐Battrawy

et al. 2019

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

Short QT syndrome (SQTS) predisposes afflicted patients to sudden cardiac death. Until now, only one drug—quinidine—has been shown to be effective in patients with SQTS type 1(SQTS1). The objective of this study was to use human‐induced pluripotent stem cell–derived cardiomyocytes (hiPSC‐CMs) from a patient with SQTS1 to search for potentially effective drugs for the treatment of SQTS1 patients. Patch clamp and single‐cell contraction measurements were employed to assess drug effects. Ivabradine, mexiletine, and ajmaline but not flecainide, ranolazine, or amiodarone prolonged the action potential duration (APD) in hiPSC‐CMs from an SQTS1 patient. Ivabradine, ajmaline, and mexiletine inhibited KCNH2 channel currents significantly, which may underlie their APD‐prolonging effects. Under proarrhythmic epinephrine stimulation in spontaneously beating SQTS1 hiPSC‐CMs, ivabradine, mexiletine, and ajmaline but not flecainide reduced the epinephrine‐induced arrhythmic events. The results demonstrate that ivabradine, ajmaline, and mexiletine may be candidate drugs for preventing tachyarrhythmias in SQTS1 patients.

show abstract

Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Mexiletinementioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Drug Testing in Human‐Induced Pluripotent Stem Cell–Derived Cardiomyocytes From a Patient With Short QT Syndrome Type 1

Zhao

El‐Battrawy

et al. 2019

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

show abstract

“…10) Recently, mexiletine was demonstrated to significantly reduce the occurrence of polymorphic VT in pharmacological models of LQT2 in isolated rabbit hearts. 11) Our experience of VT suppression by oral mexiletine in an old LQT2 patient on regular hemodialysis strengthened the evidence. More cases or lager clinical studies were needed to explore its application for general LQT2 patients.…”

Section: Discussionmentioning

confidence: 67%

Mexiletine Suppressed Recurrent Ventricular Tachycardia Triggered by Hemodialysis in an Old Patient with LQT2

Kang

Wei

2019

Int. Heart J.

View full text Add to dashboard Cite

The first onset of cardiac event of long QT syndrome (LQTS) was at young age and caused by emotional or physical triggers. We presented a 64-year-old woman who experienced recurrent ventricular arrhythmia after hemodialysis initiation because of end-stage renal disease. Persistent prolonged QTc interval and diagnosis of inherited LQT2 were missed at her first 3 years of hemodialysis. The patient was beta-blocker nonresponder for ventricular arrhythmias suppression and experienced multiple ICD discharge. We reported an inherited LQT2 case with uncommon clinical manifestations and the successful experience of mexiletine use in such a patient.

show abstract

Relevance of mexiletine in the era of evolving antiarrhythmic therapy of ventricular arrhythmias

Alhourani,

Wolfes,

Könemann

et al. 2024

Clin Res Cardiol

Self Cite

View full text Add to dashboard Cite

Despite impressive developments in the field of ventricular arrhythmias, there is still a relevant number of patients with ventricular arrhythmias who require antiarrhythmic drug therapy and may, e.g., in otherwise drug and/or ablation refractory situations, benefit from agents known for decades, such as mexiletine. Through its capability of blocking fast sodium channels in cardiomyocytes, it has played a minor to moderate antiarrhythmic role throughout the recent decades. Nevertheless, certain patients with structural heart disease suffering from drug-refractory, i.e., mainly amiodarone refractory ventricular arrhythmias, as well as those with selected forms of congenital long QT syndrome (LQTS) may nowadays still benefit from mexiletine. Here, we outline mexiletine’s cellular and clinical electrophysiological properties. In addition, the application of mexiletine may be accompanied by various potential side effects, e.g., nausea and tremor, and is limited by several drug-drug interactions. Thus, we shed light on the current therapeutic role of mexiletine for therapy of ventricular arrhythmias and discuss clinically relevant aspects of its indications based on current evidence. Graphical abstract

show abstract

Broad antiarrhythmic effect of mexiletine in different arrhythmia models

Abstract: Acute infusion of mexiletine significantly reduced the occurrence of polymorphic VT in the presence of pharmacologically simulated LQTS. Furthermore, mexiletine demonstrated potent antiarrhythmic properties in a model of SQTS and in AF.

Cited by 24 publications

References 19 publications

Drug Testing in Human‐Induced Pluripotent Stem Cell–Derived Cardiomyocytes From a Patient With Short QT Syndrome Type 1

Drug Testing in Human‐Induced Pluripotent Stem Cell–Derived Cardiomyocytes From a Patient With Short QT Syndrome Type 1

Mexiletine Suppressed Recurrent Ventricular Tachycardia Triggered by Hemodialysis in an Old Patient with LQT2

Relevance of mexiletine in the era of evolving antiarrhythmic therapy of ventricular arrhythmias

Contact Info

Product

Resources

About