1P270 Effects of H2 blocker famotidine on HERG current and action potential of cardiac ventricular nryocytes

• Published in: Journal of Pharmacological Sciences 2003, Vol.91 (suppl.1), p.155-155
• Main Authors: Nao Uchimura, Junko Matsuo, Gong Qi, Shin-ichi Nagayama, Koichi Kuwano, Ryoichi Nagata, Go Kito
• Format: Article
• Language: Japanese
• ISSN: 1347-8613

Recently, it was reported that a H2 blocker famotidine cause QT prolongation leading to torsades de pointes (TdP) in human. Furthermore it has been known that female gender is a risk factor for drug-induced TdP. The aim of this study is to determine whether famotidine has a cardiac proarrhythmic effect and to evaluate how sex honnones influence on effect of famotigine. [Methods] lon current : In HERG (human ether a go-go related gene)-transfected cells, CHO-K1, ion currents were measured by the Patch-clamp technique. Action potential (AP) : The heart of male guinea pigs (4-12 weeks) was harvested and perfused with Ca2+ free Tyrode solution containing collagenase through the coronary artery with a Langendorff apparatus. The left ventricular was cut out and dispersed to isolate ventricular myocytes. AP was measured by the Patch-clamp technique. [Results and Conclusion] Famotidine (10-100 μM) prolonged APD90 by 15-46%, but not HERG current. However, pretreating 17-β-estradiol (1-100μM), famotidine (30μM) did not affect HERG current. These results demonstrate that 17-β-estradiol had not interaction with famotidine on HERG current. But, additive studies should need to elucidate the interaction with sex hormones regarding a cardiac proarrhythmic effect of famotidine.