Effect of terfenadine and KW-4679, a novel antiallergic compound, on action potential of guinea pig ventricular myocytes.
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.
Kato
Y
Y
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Mori
T
T
Ohmori
K
K
Ichimura
M
M
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D003990:Dibenzoxepins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D000069605:Olopatadine Hydrochloride; D016593:Terfenadine / Q000494:pharmacology*
D018926:Anti-Allergic Agents; D003990:Dibenzoxepins; D000069605:Olopatadine Hydrochloride; D016593:Terfenadine