ArticleBritish journal of pharmacology2007
State dependent dissociation of HERG channel inhibitors.
Article in British journal of pharmacology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.
- Domperidone and Risk of Ventricular Arrhythmia and Cardiac Death: A Systematic Review and Meta-analysis.Clinical drug investigation · 2016Pooled it
- A hERG Blocker Facilitates KbioRxiv : the preprint server for biology · 2026Article
- The Methanesulfonamide Group: Bright and Dark Sides of hERG Potassium Channel Inhibition.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Multi-laboratory comparisons of manual patch clamp hERG data generated using standardized protocols and following ICH S7B Q&A 2.1 best practices.Scientific reports · 2025Article
- Article
- Harnessing AlphaFold to reveal hERG channel conformational state secrets.bioRxiv : the preprint server for biology · 2025Article
- Optimizing experimental designs for model selection of ion channel drug-binding mechanisms.Philosophical transactions. Series A, Mathematical, physical, and engineering sciences · 2025Article
- Integrating drug effects on individual cardiac ionic currents and cardiac action potentials to understand nonclinical translation to clinical ECG changes.Frontiers in pharmacology · 2025Article
- Design, synthesis, and biological evaluation of a novel series of 1,2,4-oxadiazole inhibitors of SLACK potassium channels: Identification of in vitro tool VU0935685.Bioorganic & medicinal chemistry · 2023Article
- Structural modeling of hERG channel-drug interactions using Rosetta.Frontiers in pharmacology · 2023Article
- Importance of modelling hERG binding in predicting drug-induced action potential prolongations for drug safety assessment.Frontiers in pharmacology · 2023Article
- Metabolic and electrolyte abnormalities as risk factors in drug-induced long QT syndrome.Biophysical reviews · 2022Review
- Translational Models and Tools to Reduce Clinical Trials and Improve Regulatory Decision Making for QTc and Proarrhythmia Risk (ICH E14/S7B Updates).Clinical pharmacology and therapeutics · 2021Review
- Influence of Kv11.1 (hERG1) KPflugers Archiv : European journal of physiology · 2021Article
- Cardiac hERG KHandbook of experimental pharmacology · 2021Article
- A systematic strategy for estimating hERG block potency and its implications in a new cardiac safety paradigm.Toxicology and applied pharmacology · 2020Article
- When Does the ICJournal of chemical information and modeling · 2020Article
- The macrolide drug erythromycin does not protect the hERG channel from inhibition by thioridazine and terfenadine.Physiological reports · 2020Article
- Allosteric Coupling Between Drug Binding and the Aromatic Cassette in the Pore Domain of the hERG1 Channel: Implications for a State-Dependent Blockade.Frontiers in pharmacology · 2020Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeInhibition of HERG channels prolongs the ventricular action potential and the QT interval with the risk of torsade de pointes arrhythmias and sudden cardiac death. Many drugs induce greater inhibition of HERG channels when the cell membrane is depolarized frequently. The dependence of inhibition on the pulsing rate may yield different IC(50) values at different frequencies and thus affect the quantification of HERG channel block. We systematically compared the kinetics of HERG channel inhibition and recovery from block by 8 blockers at different frequencies. EXPERIMENTAL APPROACH: HERG channels were expressed heterologously in Xenopus oocytes and currents were measured with the two-electrode voltage clamp technique. KEY
resultsFrequency-dependent block was observed for amiodarone, cisapride, droperidol and haloperidol (group 1) whereas bepridil, domperidone, E-4031 and terfenadine (group 2) induced similar pulse-dependent block at all frequencies. With the group 1 compounds, HERG channels recovered from block in the presence of drug (recovery being voltage-dependent). No substantial recovery from block was observed with the second group of compounds. Washing out of bepridil, domperidone, E-4031 and terfenadine was substantially augmented by frequent pulsing. Mutation D540K in the HERG channel (which exhibits reopening at negative voltages) facilitated recovery from block by these compounds at -140 mV. CONCLUSION AND IMPLICATIONS: Drug molecules dissociate at different rates from open and closed HERG channels ('use-dependent' dissociation). Our data suggest that apparently 'trapped' drugs (group 2) dissociated from the open channel state whereas group 1 compounds dissociated from open and resting states.
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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.