Yoshimitsu Kato, Tatsuya Mori, Kenji Ohmori and Michio Ichimura (*)
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411, Japan
(*) To whom correspondence should be addressed.
Abstract: It has been reported that terfenadine caused torsade de pointes ventricular arrhythmias. The prolongation of action potential duration (APD) in ventricles is considered to be one of the mechanisms of this adverse effect. We examined the effect of antiallergic drugs, terfenadine and KW-4679 ((Z)-11-[3-(dimethylamino)propylidene]- 6,11-dihydrodibenz[b,e]oxepin-2-acetic acid hydrochloride), on action potentials in isolated guinea pig ventricular myocytes. Terfenadine (30 nM - 1 microM) increased APD in a concentration-dependent manner. On the other hand, KW-4679 (0.1 microM - 100 microM) exerted no significant effects on action potential parameters. These results present no evidence that KW-4679 has the possibility to cause ventricular arrhythmias.
Keywords:
Antiallergic drug, Action potential, Ventricular myocyte