ArticleThe Journal of general physiology2015
A general mechanism for drug promiscuity: Studies with amiodarone and other antiarrhythmics.
Article in The Journal of general physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Effect of the Membrane Environment on Pharmacologic Inhibition of hERG KJACC. Clinical electrophysiology · 2025Article
- Bio-spectroscopic investigation linking changes of retinal structure with short-term administration of Amiodarone and revealing the ameliorative effect of vitamin E supplementation.Scientific reports · 2024Article
- Intrinsic Lipid Curvature and Bilayer Elasticity as Regulators of Channel Function: A Comparative Single-Molecule Study.International journal of molecular sciences · 2024Article
- Dimeric Tubulin Modifies Mechanical Properties of Lipid Bilayer, as Probed Using Gramicidin A Channel.International journal of molecular sciences · 2024Article
- Screening for bilayer-active and likely cytotoxic molecules reveals bilayer-mediated regulation of cell function.The Journal of general physiology · 2023Article
- Phenotypic drug discovery: recent successes, lessons learned and new directions.Nature reviews. Drug discovery · 2022Review
- Capsaicin as an amphipathic modulator of NaChannels (Austin, Tex.) · 2022Article
- Nebivolol as a Potent TRPM8 Channel Blocker: A Drug-Screening Approach through Automated Patch Clamping and Ligand-Based Virtual Screening.Membranes · 2022Article
- Common Structural Pattern for Flecainide Binding in Atrial-Selective KPharmaceutics · 2022Article
- Asymmetric effects of amphipathic molecules on mechanosensitive channels.Scientific reports · 2022Article
- Cannabidiol increases gramicidin current in human embryonic kidney cells: An observational study.PloS one · 2022Observational
- Mechanisms underlying drug-mediated regulation of membrane protein function.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Cannabidiol inhibits the skeletal muscle Nav1.4 by blocking its pore and by altering membrane elasticity.The Journal of general physiology · 2021Article
- Assessing the Perturbing Effects of Drugs on Lipid Bilayers Using Gramicidin Channel-BasedJournal of medicinal chemistry · 2020Article
- Synthesis and evaluation of resveratrol derivatives as fetal hemoglobin inducers.Bioorganic chemistry · 2020Article
- Molecular Mechanism for Gramicidin Dimerization and Dissociation in Bilayers of Different Thickness.Biophysical journal · 2019Article
- Multiple neurosteroid and cholesterol binding sites in voltage-dependent anion channel-1 determined by photo-affinity labeling.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2019Article
- Antidepressants are modifiers of lipid bilayer properties.The Journal of general physiology · 2019Article
- Article
- Lipid signaling to membrane proteins: From second messengers to membrane domains and adapter-free endocytosis.The Journal of general physiology · 2018Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Amiodarone is a widely prescribed antiarrhythmic drug used to treat the most prevalent type of arrhythmia, atrial fibrillation (AF). At therapeutic concentrations, amiodarone alters the function of many diverse membrane proteins, which results in complex therapeutic and toxicity profiles. Other antiarrhythmics, such as dronedarone, similarly alter the function of multiple membrane proteins, suggesting that a multipronged mechanism may be beneficial for treating AF, but raising questions about how these antiarrhythmics regulate a diverse range of membrane proteins at similar concentrations. One possible mechanism is that these molecules regulate membrane protein function by altering the common environment provided by the host lipid bilayer. We took advantage of the gramicidin (gA) channels' sensitivity to changes in bilayer properties to determine whether commonly used antiarrhythmics--amiodarone, dronedarone, propranolol, and pindolol, whose pharmacological modes of action range from multi-target to specific--perturb lipid bilayer properties at therapeutic concentrations. Using a gA-based fluorescence assay, we found that amiodarone and dronedarone are potent bilayer modifiers at therapeutic concentrations; propranolol alters bilayer properties only at supratherapeutic concentration, and pindolol has little effect. Using single-channel electrophysiology, we found that amiodarone and dronedarone, but not propranolol or pindolol, increase bilayer elasticity. The overlap between therapeutic and bilayer-altering concentrations, which is observed also using plasma membrane-like lipid mixtures, underscores the need to explore the role of the bilayer in therapeutic as well as toxic effects of antiarrhythmic agents.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.