antibiotics (including quinolones and macrolides). Although there exist other potential targets for cardiac adverse effects, the vast majority of drugs associated with acquired QT prolongation are known to interact with the hERG potassium channel. One of the main reasons for this phenomenon is the larger inner vestibule of the hERG channel, thus providing more space for many different drug classes to bind and block this potassium channel. hERG containing channels are blocked by amiodarone, and it does prolong the QT interval, but its multiple other antiarrhythmic effects prevent this from causing torsades de pointes. Thioridazine causes peculiarly severe QTc prolongation by blocking hERG and was withdrawn by the manufacturer for this reason. Drug development considerations Due to the documented potential of QT-interval-prolonging drugs, the United States Food and Drug Administration issued recommendations for the establishment of a cardiac safety profile during pre-clinical drug development: ICH S7B. The nonclinical evaluation of the potential for delayed ventricular repolarization (QT interval prolongation) by human pharmaceuticals, issued as CHMP/ICH/423/02, adopted by CHMP in May 2005. Preclinical hERG studies should be accomplished in GLP environment. Naming The hERG gene was first named and described in a paper by Jeff Warmke and Barry Ganetzky, then both at the University of Wisconsin–Madison. The hERG gene is the human homolog of the Ether-à-go-go gene found in the Drosophila fly; Ether-à-go-go was named in the 1960s by William D. Kaplan and William E. Trout, III, while at the City of Hope Hospital in Duarte, California. When flies with mutations in the Ether-à-go-go gene are anaesthetised with ether, their legs start to shake, like the dancing at the then popular Whisky a Go Go nightclub in West Hollywood, California. Interactions HERG has been shown to interact with the 14-3-3 epsilon protein, encoded by YWHAE. See also Voltage-gated potassium channel References Further reading External links GeneReviews/NIH/NCBI/UW entry on Romano-Ward Syndrome International Conference on Harmonization Drosophila flybase entry for erg Special K: Primate-specific Potassium Channel Variant Implicated in Schizophrenia - Schizophrenia Research Forum. Ion channels PAS-domain-containing proteins