ArticleBritish journal of pharmacology2005
Blockade of HERG cardiac K+ current by antifungal drug miconazole.
Article in British journal of pharmacology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 44 citations in OpenAlex.
- Role of the calcium-sensing receptor in regulating vascular function.Journal of cell communication and signaling · 2025Review
- Protection of pancreatic islets from oxidative cell death by a peripherally-active morphinan with increased drug safety.Molecular metabolism · 2023Article
- Fluorescent membrane potential assay for drug screening on Kv10.1 channel: identification of BL-1249 as a channel activator.Frontiers in pharmacology · 2023Article
- The Anti-Fungal Activity of Nitropropenyl Benzodioxole (NPBD), a Redox-Thiol Oxidant and Tyrosine Phosphatase Inhibitor.Antibiotics (Basel, Switzerland) · 2022Article
- Evaluation of combination therapy for Burkholderia cenocepacia lung infection in different in vitro and in vivo models.PloS one · 2017Article
- Inhibition of hERG potassium channel by the antiarrhythmic agent mexiletine and its metabolite m-hydroxymexiletine.Pharmacology research & perspectives · 2015Article
- Characterization of a novel multifunctional resveratrol derivative for the treatment of atrial fibrillation.British journal of pharmacology · 2014Article
- Escitalopram block of hERG potassium channels.Naunyn-Schmiedeberg's archives of pharmacology · 2014Article
- Integrated analysis of drug-induced gene expression profiles predicts novel hERG inhibitors.PloS one · 2013Article
- Trapping and dissociation of propafenone derivatives in HERG channels.British journal of pharmacology · 2011Article
- State-dependent blockade of human ether-a-go-go-related gene (hERG) K(+) channels by changrolin in stably transfected HEK293 cells.Acta pharmacologica Sinica · 2010Article
- Transfer of rolf S3-S4 linker to HERG eliminates activation gating but spares inactivation.Biophysical journal · 2009Article
- Torsades de pointes associated with methadone and voriconazole.BMJ case reports · 2009Article
- Coexistence of hERG current block and disruption of protein trafficking in ketoconazole-induced long QT syndrome.British journal of pharmacology · 2008Article
- Torsades de Pointes ventricular tachycardia in a pediatric patient treated with fluconazole.Pediatric cardiology · 2008Article
- State dependent dissociation of HERG channel inhibitors.British journal of pharmacology · 2007Article
- Comparison of HERG channel blocking effects of various beta-blockers-- implication for clinical strategy.British journal of pharmacology · 2006Article
- Effects of the antifungal antibiotic clotrimazole on human cardiac repolarization potassium currents.British journal of pharmacology · 2006Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
1. Miconazole, an imidazole antifungal agent, is associated with acquired long QT syndrome and ventricular arrhythmias. Miconazole increases the plasma concentration of QT-prolonging drugs by inhibiting the hepatic cytochrome P450 metabolic pathway, but whether it has direct effects on cardiac ion channels has not been elucidated. 2. To determine the mechanism underlying these clinical findings, we investigated the effect of miconazole on human ether-a-go-go-related gene (HERG) K+ channels. 3. HERG channels were heterologously expressed in human embryonic kidney 293 (HEK293) cells and whole-cell currents were recorded using a patch-clamp technique (23 degrees C). 4. Miconazole inhibited HERG peak tail current in a concentration-dependent manner (0.4-40 microM) with an IC50 of 2.1 microM (n=3-5 cells at each concentration, Hill coefficient 1.2). HERG block was not frequency-dependent. It required channel activation, occurred rapidly, and had very slow dissociation properties. 5. The activation curve was shifted in a negative direction (V(1/2): -9.5+/-2.3 mV in controls and -15.3+/-2.4 mV after 4 microM miconazole, P<0.05, n=6). Miconazole did not change other channel kinetics (activation, deactivation, onset of inactivation, recovery from inactivation, steady-state inactivation). 6. The S6 domain mutation, F656C, abolished the inhibitory action of miconazole on HERG current indicating that miconazole preferentially binds to an aromatic amino-acid residue within the pore-S6 region. 7. Our findings indicate that miconazole causes HERG channel block by binding to a common drug receptor, and this involves preferential binding to activated channels. Thus, miconazole prolongs the QT interval by direct inhibition of HERG channels.
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