Comparative Evaluation of HERG Currents and QT Intervals following Challenge with Suspected Torsadogenic and Nontorsadogenic Drugs

• Published in: The Journal of pharmacology and experimental therapeutics 2006-03, Vol.316 (3), p.1098-1106
• Main Authors: Katchman, Alexander N, Koerner, John, Tosaka, Toshimasa, Woosley, Raymond L, Ebert, Steven N
• Format: Article
• Language: English
• Subjects: Animals; Arsenicals - pharmacology; Cells, Cultured; Electrocardiography - drug effects; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels - antagonists & inhibitors; Ether-A-Go-Go Potassium Channels - physiology; Haloperidol - pharmacology; Humans; Loratadine - pharmacology; Lovastatin - pharmacology; Methadone - pharmacology; Oxides - pharmacology; Pentamidine - pharmacology; Potassium Channel Blockers - pharmacology; Rabbits; Terfenadine - pharmacology; Torsades de Pointes - chemically induced
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.105.093393

The purpose of the present study was to comparatively evaluate human HERG currents and QT intervals following challenge with suspected torsadogenic and nontorsadogenic drugs. Various concentrations of 14 different drugs were initially evaluated in terms of their relative potency to block I HERG in stably transfected human embryonic kidney cells. Four general categories of drugs were identified: high-potency blockers (IC 50 < 0.1 μM) included lidoflazine, terfenadine, and haloperidol; moderate-potency blockers (0.1 μM < IC 50 < 1 μM) included sertindole, thioridazine, and prenylamine; low-potency blockers (IC 50 > 1 μM) included propafenone, loratadine, pyrilamine, lovastatin, and chlorpheniramine; and ineffective blockers (IC 50 > 300 μM) included cimetidine, pentamidine, and arsenic trioxide. All measurements were performed using similar conditions and tested acute drug effects only (