Preclinical testing of drug-induced proarrhythmia: value of transgenic models

Cardiovasc Hematol Agents Med Chem. 2007 Oct;5(4):289-94. doi: 10.2174/187152507782109881.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Action Potentials / drug effects*
  • Animals
  • Animals, Genetically Modified
  • Anti-Arrhythmia Agents / adverse effects*
  • Arrhythmias, Cardiac / chemically induced*
  • Disease Models, Animal
  • Drug Design
  • Humans
  • Mice
  • Potassium Channels / genetics
  • Sodium Channels / genetics

Substances

  • Anti-Arrhythmia Agents
  • Potassium Channels
  • Sodium Channels