title: Drug-induced block of cardiac HERG potassium channels and development of torsade de pointes arrhythmias: the case of antipsychotics.
abstract: The prolongation of the cardiac repolarization process, a result of the blocking of the Human Ether-ago-go Related Gene potassium channel, is an undesired accessory property shared by many pharmacological classes of non-cardiovascular drugs. Often the delayed cardiac repolarization process can be identified by a prolongation of the QT interval of the electrocardiograph. In these conditions, premature action potentials can trigger a dangerous polymorphic ventricular tachyarrhythmia, known as torsade de pointes, which occasionally can result in lethal ventricular fibrillation. In this work, brief descriptions of the electrophysiological basis of torsade de pointes and of the several pharmacological classes of torsadogenic drugs are given. Attention is focused on antipsychotics, with a deeper overview on the experimental and clinical reports about their torsadogenic properties.
authors.affiliation: Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università degli Studi di Pisa, Via Bonanno 6, I-56126, Pisa, Italy. calderone@farm.unipi.it
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Calderone
authors.forename: Lara
authors.initials: L
authors.lastname: Testai
authors.forename: Enrica
authors.initials: E
authors.lastname: Martinotti
authors.forename: Mario
authors.initials: M
authors.lastname: Del Tacca
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Breschi
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000145:classification / Q000627:therapeutic use; D006801:Humans; D007558:Italy; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000187:drug effects*; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D014150:Antipsychotic Agents; D024642:Potassium Channels, Voltage-Gated