ArticleToxicology reports2026
Neuronal safety of Kv11.1 blockers: Patch-clamp and in vitro evaluation with physiologically based pharmacokinetic (PBPK) modeling.
Article in Toxicology reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Class III antiarrhythmic drugs are indispensable for cardiac rhythm control, yet their susceptibility to clinically used ion channel modulating drugs remains insufficiently characterized. Because Kv11.1 channels are present in neurons and glia, their pharmacological engagement may influence excitability and cell viability. Here, we investigated Sotalol, Ibutilide, and Amiodarone, three clinically used Kv11.1 active compounds with distinct lipophilicity profiles, using an integrated strategy that combines whole-cell patch-clamp electrophysiology, cell viability assays, and physiologically based pharmacokinetic (PBPK) modeling in neuron-like SH-SY5Y cells, a human model widely used for neurotoxicity and ion-channel studies. Sotalol produced minimal electrophysiological changes, whereas Ibutilide caused moderate suppression of outward K⁺ currents, and Amiodarone did not show acute effects under our patch-clamp conditions. However, Amiodarone induced pronounced morphological changes and loss of viability
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