In vitro and in vivo models for testing arrhythmogenesis in drugs.
The steadily increasing list of drugs associated with prolongation of the QT interval and torsades de pointes (TdP) constitute a medical problem of major concern. Hence, there is a need at an early stage to identify drug candidates with an inherent capacity to induce repolarization-related proarrhythmias, avoiding exposure of large populations to potentially harmful drugs. Furthermore, the availability of clinically relevant and predictive animal models should reduce the risk that effective and potentially life-saving drugs never reach the market. This review will discuss the pros and cons of some in vivo and in vitro animal models for assessing proarrhythmia liability.
Carlsson
L
L
AstraZeneca R&D Mölndal, Integrative Pharmacology, Mölndal, Sweden. leif.g.carlsson@astrazeneca.com
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002415:Cats; D004195:Disease Models, Animal; D004285:Dogs; D064420:Drug-Related Side Effects and Adverse Reactions; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006327:Heart Block / Q000139:chemically induced; D006352:Heart Ventricles / Q000187:drug effects; D008133:Long QT Syndrome / Q000139:chemically induced*; D008729:Methoxamine / Q000494:pharmacology; D011817:Rabbits; D016171:Torsades de Pointes / Q000139:chemically induced*
D000316:Adrenergic alpha-Agonists; D008729:Methoxamine