Inhibitory effects of the antihistamines epinastine, terfenadine, and ebastine on potassium currents in rat ventricular myocytes.
We examined and compared the inhibitory effects of three non-sedating antihistamines, terfenadine, ebastine, and epinastine, on delayed rectifier potassium current (IK) and transient outward potassium current (Ito) of rat isolated ventricular myocytes, using a patch clamp technique. Terfenadine, ebastine and epinastine were found to inhibit IK with IC50 values of 5.96, 15.3 and 145 microM, respectively. Ito was suppressed by epinastine with an IC50 value of 69.5 microM. The order of arrhythmogenicity, assessed by the inhibition of IK, was ranked as terfenadine > ebastine > epinastine, consistent with that of the potencies of each drug for QT prolongation reported in rats.
Ohtani
H
H
Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, Japan.
Hanada
E
E
Hirota
M
M
Sato
H
H
Kotaki
H
H
Sawada
Y
Y
Uemura
H
H
Nakaya
H
H
Iga
T
T
D000818:Animals; D002090:Butyrophenones / Q000494:pharmacology*; D003984:Dibenzazepines / Q000494:pharmacology*; D004594:Electrophysiology; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016593:Terfenadine / Q000494:pharmacology*
D002090:Butyrophenones; D003984:Dibenzazepines; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D010880:Piperidines; D015221:Potassium Channels; D016593:Terfenadine; C053090:epinastine; C058249:ebastine