Anticholinergic antiparkinson drug orphenadrine inhibits HERG channels: block attenuation by mutations of the pore residues Y652 or F656
@article{Scholz2007AnticholinergicAD, title={Anticholinergic antiparkinson drug orphenadrine inhibits HERG channels: block attenuation by mutations of the pore residues Y652 or F656}, author={Eberhard P. Scholz and Franziska M. Konrad and Daniel L. Wei{\ss} and Edgar Zitron and Claudia Kiesecker and Ramona Bloehs and Martin Kulzer and Dierk Thomas and Sven Kathöfer and Alexander Bauer and Martin H. Maurer and Gunnar Seemann and Hugo A. Katus and Christoph Karle}, journal={Naunyn-Schmiedeberg's Archives of Pharmacology}, year={2007}, volume={376}, pages={275-284} }
The anticholinergic antiparkinson drug orphenadrine is an antagonist at central and peripheral muscarinic receptors. Orphenadrine intake has recently been linked to QT prolongation and Torsade-de-Pointes tachycardia. So far, inhibitory effects on IKr or cloned HERG channels have not been examined. HERG channels were heterologously expressed in a HEK 293 cell line and in Xenopus oocytes and HERG current was measured using the whole cell patch clamp and the double electrode voltage clamp…
13 Citations
Anesthetic drug midazolam inhibits cardiac human ether-à-go-go-related gene channels: mode of action
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It is shown that the anesthetic midazolam is a low-affinity inhibitor of cardiac hERG channels without additional effects on channel surface expression.
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Whereas inhibitory effects of duloxetine seem negligible under therapeutically relevant concentrations, hERG block should be considered in cases of dULoxetines overdose and when administering dulxetine to patients susceptible to drug-induced QT prolongation.
Involvement of voltage-gated sodium channels blockade in the analgesic effects of orphenadrine
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- BiologyDrug design, development and therapy
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Using the double-electrode voltage clamp technique, midazolam acted as a typical open-channel inhibitor with rapid onset of block and without frequency dependence of block, and is an open channel inhibitor of cardiac Kv1.5 channels.
Influence of orphenadrine upon the protective activity of various antiepileptics in the maximal electroshock-induced convulsions in mice.
- Biology, MedicinePharmacological reports : PR
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Current pharmacogenomic studies on hERG potassium channels.
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Collation, assessment and analysis of literature in vitro data on hERG receptor blocking potency for subsequent modeling of drugs' cardiotoxic properties
- Biology, ChemistryJournal of applied toxicology : JAT
- 2009
The main objective of this work was to collect and assess the hERG IC50 data available in accessible scientific literature to provide a high‐quality data set for further studies.
Orphenadrine induces secondarily generalized convulsive status epilepticus in rats
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Predicting the potency of hERG K+ channel inhibition by combining 3D-QSAR pharmacophore and 2D-QSAR models
- Biology, ChemistryJournal of Molecular Modeling
- 2011
An ensemble of 3D-QSAR pharmacophore models was constructed to provide insight into the determinants of the interactions between the hERG K+ channel and channel inhibitors, and this final model outperformed any other individual model, showing the highest predictive ability and the lowest deviation.
Similarity-Based Classifier Using Topomers to Provide a Knowledge Base for hERG Channel Inhibition
- Computer Science, BiologyJ. Chem. Inf. Model.
- 2009
It is shown that the similarity property principle can be applied to predict ADMET properties, exemplified on the case of hERG K+ channel inhibition, and is achievable for database sizes of about 10,000 structurally diverse molecules.
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