Key result
Cenobamate shortens ventricular APD90 by ~29% via peak INa inhibition, signaling potential proarrhythmic risk.
Why the study?
Cenobamate causes side effects including QTc interval shortening, prompting an in vitro evaluation of its cardiac safety pharmacology across human cardiac ion channels.
Does cenobamate inhibit human cardiac ion channels and alter action potential duration in vitro?
Population
HEK293T cells expressing human cardiac ion channels, Ncyte ventricular cardiomyocytes, and simulated strands of 50 cardiomyocytes
Comparison
Cenobamate exposure across cardiac models
Design
In vitro cardiac safety pharmacology and simulation study
Authors
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May theoretically promote reentry in diseased myocardium; leaves open clinical arrhythmia risk in epilepsy patients.
Does cenobamate inhibit human cardiac ion channels and alter action potential duration in vitro?
Effect estimate: IC50 87.6 µM
Cenobamate exhibits local anesthetic-like properties by inhibiting cardiac sodium channels, which may shorten the QT interval and theoretically promote reentry arrhythmias in ischemic or pathological myocardium.
Mateias et al. (2024) studied In vitro cardiac safety pharmacology. Cenobamate vs. Control (vehicle/DMSO) was evaluated on Peak INa inhibition (IC50) (IC50 87.6 µM). Cenobamate significantly inhibited peak INa (IC50 87.6 µM) and reduced APD90 by 28.6% at 200 µM, raising the theoretical possibility of cardiac arrhythmia induction in pathological myocardium.
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