Abstract
Drug-induced proarrhythmia is a serious medical problem that causes relevant morbidity and mortality. It is also a relevant problem for the development of novel pharmacological compounds. Therefore, there is a need for sensitive, specific and high-throughput preclinical tests to detect a risk for drug-induced proarrhythmia early in the development of new drugs. The review focuses on the potential role of transgenic models with altered repolarisation but without overt structural heart disease for drug-induced proarrhythmia screening. Today, selected murine models with alterations in K+, Na+ channels and ankyrin are available. In the future, transgenic rabbit and Zebra fish models may also be used.
Keywords: Drug-induced proarrhythmia, repolarisation, long QT syndrome, action potential prolongation, torsades de pointes, transgenic model, experimental model, ion channels
Cardiovascular & Hematological Agents in Medicinal Chemistry
Title: Preclinical Testing of Drug-Induced Proarrhythmia: Value of Transgenic Models
Volume: 5 Issue: 4
Author(s): L. Fabritz, G. Breithardt and P. Kirchhof
Affiliation:
Keywords: Drug-induced proarrhythmia, repolarisation, long QT syndrome, action potential prolongation, torsades de pointes, transgenic model, experimental model, ion channels
Abstract: Drug-induced proarrhythmia is a serious medical problem that causes relevant morbidity and mortality. It is also a relevant problem for the development of novel pharmacological compounds. Therefore, there is a need for sensitive, specific and high-throughput preclinical tests to detect a risk for drug-induced proarrhythmia early in the development of new drugs. The review focuses on the potential role of transgenic models with altered repolarisation but without overt structural heart disease for drug-induced proarrhythmia screening. Today, selected murine models with alterations in K+, Na+ channels and ankyrin are available. In the future, transgenic rabbit and Zebra fish models may also be used.
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Cite this article as:
Fabritz L., Breithardt G. and Kirchhof P., Preclinical Testing of Drug-Induced Proarrhythmia: Value of Transgenic Models, Cardiovascular & Hematological Agents in Medicinal Chemistry 2007; 5 (4) . https://dx.doi.org/10.2174/187152507782109881
DOI https://dx.doi.org/10.2174/187152507782109881 |
Print ISSN 1871-5257 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6182 |
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