Investigating the Cardiotoxicity of N-n-Butyl Haloperidol Iodide: Inhibition Mechanisms on hERG Channels.

The human Ether-à-go-go-Related Gene (hERG) encodes a protein responsible for forming the alpha subunit of the IKr channel, which plays a crucial role in cardiac repolarization. The proper functioning of hERG channels is paramount in maintaining a normal cardiac rhythm. Inhibition of these channels can result in the prolongation of the QT interval and potentially life-threatening arrhythmias. Cardiotoxicity is a primary concern in the field of drug development. N-n-Butyl haloperidol iodide (F2), a derivative of haloperidol, has been investigated for its therapeutic potential. However, the impact of this compound on cardiac toxicity, specifically on hERG channels, remains uncertain. This study employs computational and experimental methodologies to examine the inhibitory mechanisms of F2 on hERG channels. Molecular docking and molecular dynamics simulations commonly used techniques in computational biology to predict protein-ligand complexes' binding interactions and stability. In the context of the F2-hERG complex, these methods can provide valuable insights into the potential binding modes and strength of interaction between F2 and the hERG protein. On the other hand, electrophysiological assays are experimental techniques used to characterize the extent and nature of hERG channel inhibition caused by various compounds. By measuring the electrical activity of the hERG channel in response to different stimuli, these assays can provide important information about the functional effects of ligand binding to the channel. The study's key findings indicate that F2 interacts with the hERG channel by forming hydrogen bonding, π-cation interactions, and hydrophobic forces. This interaction leads to the inhibition of hERG currents in a concentration-dependent manner, with an IC

Informations de copyright

Copyright © 2024. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest As the corresponding author of the manuscript entitled “Investigating the Cardiotoxicity of N-n-Butyl Haloperidol Iodide: Inhibition Mechanisms on hERG Channels,” I declare that there are no conflicts of interest associated with this submission. Neither I nor any of my co-authors have any financial, personal, or other relationships with other people or organizations that could inappropriately influence or bias our work. Specifically: We confirm that the manuscript is original, has not been previously published, and is not under consideration for publication elsewhere. All authors have approved the final manuscript and agree with its submission to Toxicology Declaration of Competing Interest The authors declare that they have no financial conflicts of interest or personal relationships that could have influenced the findings reported in this paper.