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Inhibitory Effects of Cenobamate on Multiple Human Cardiac Ion Channels and Possible Arrhythmogenic Consequences.

Biomolecules

December 2024

Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Splaiul Independentei 91-95, 050095 Bucharest, Romania.

Cenobamate is a novel third-generation antiepileptic drug used for the treatment of focal onset seizures and particularly for multi-drug-resistant epilepsy; it acts on multiple targets: GABA receptors (EC 42-194 µM) and persistent neuronal Na currents (IC 59 µM). Side effects include QT interval shortening with >20 ms, but not <300 ms. Our in vitro cardiac safety pharmacology study was performed via whole-cell patch-clamp on HEK293T cells with persistent/inducible expression of human cardiac ion channel isoforms hNav1.

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Population Pharmacokinetics and Pharmacodynamics of Sotalol Following Expedited Intravenous Loading in Patients With Atrial Arrhythmias.

CPT Pharmacometrics Syst Pharmacol

January 2025

Division of Clinical Pharmacology, Department of Pediatrics, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, Utah, USA.

Sotalol, a class III antiarrhythmic agent, is used to maintain sinus rhythm in patients with atrial fibrillation or atrial flutter (AFIB/AFL). Despite its efficacy, sotalol's use is limited by its potential to cause life-threatening ventricular arrhythmias due to QT interval prolongation. Traditionally, sotalol administration required hospitalization to monitor these risks.

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Obesity is associated with abnormal repolarization manifested by QT interval prolongation, and oxidative stress is an important link between obesity and arrhythmias. However, the underlying electrophysiological and molecular mechanisms remain unclear. The aim of this study is to evaluate the role of obesity in potassium current in ventricular myocytes and the potential mechanism of NADPH oxidase 2 (Nox2).

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Background -Smoking is associated with arrhythmia and sudden cardiac death, but the biological mechanisms remain unclear. In electrocardiogram (ECG) recordings abnormal durations of ventricular repolarization (QT interval), atrial depolarization (P wave), and atrioventricular depolarization (PR interval and segment), predict cardiac arrhythmia and mortality. Previous analyses of the National Health and Nutrition Examination Survey (NHANES) database for associations between smoking and ECG abnormalities were incomplete.

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Background/objectives: Routine screening electrocardiograms (ECGs) prior to starting medications for attention-deficit/hyperactivity disorder (ADHD) remain controversial. This real-world study assessed corrected QT (QTc) interval data from pediatric patients who had a baseline ECG performed prior to initiating treatment with ADHD medications and ≥6 months of clinical follow-up.

Methods: A retrospective chart review of children aged 2-18 years diagnosed with ADHD with/without autism spectrum disorder (ASD) at child neurology clinics in Jordan (June 2019 and June 2021) was performed, and children were prescribed with ADHD medications to manage symptoms.

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