Effects of fluoroquinolones on HERG currents.
We have investigated the effects of four fluoroquinolones on the human ether-à-go-go-related gene (HERG) mediated K(+) currents to evaluate their potential to induce QT-prolongation. HERG currents were measured from stably transfected Chinese hamster ovary (CHO) cells by means of the patch-clamp technique. Bath application of sparfloxacin, moxifloxacin and grepafloxacin produced an inhibition of HERG outward currents at -40 mV with EC(50) of 13.5+/-0.8, 41. 2+/-2.0 and 37.5+/-3.3 microg/ml, respectively. Current inhibitions were reversible after washout of the compounds. By contrast, ciprofloxacin at concentrations of up to 100 microg/ml did not effect HERG outward currents.
Bischoff
U
U
GENION Forschungsgesellschaft, Abteistrasse 57, 20149, Hamburg, Germany. bischoff@genion-research.com
Schmidt
C
C
Netzer
R
R
Pongs
O
O
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D016466:CHO Cells; D027682:Cation Transport Proteins; D006224:Cricetinae; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D024841:Fluoroquinolones; D006801:Humans; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG
D000890:Anti-Infective Agents; D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D024841:Fluoroquinolones; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG