Effects of itopride hydrochloride on the delayed rectifier K+ and L-type CA2+ currents in guinea-pig ventricular myocytes.
The effects of itopride hydrochloride, a new drug used to regulate motility in the gastrointestinal tract, on the delayed rectifier K+ current (I(K)) and the L-type Ca2+ current (I(Ca)) were evaluated in guinea-pig ventricular myocytes at concentrations of 1, 10 and 100 microM to determine whether the drug has a proarrhythmic effect through blockade of I(K). Itopride did not affect I(K) at concentrations of 100 microM or less, and no significant effects of 1, 10 or 100 microM itopride were observed on the inward rectifier K+ current (I(K1)) responsible for the resting potential and final repolarization phase of the action potential. We next investigated the effects of itopride on L-type Ca2+ current (I(Ca)). Significant inhibition of I(Ca) was observed at itopride concentrations greater than 10 microM. These results suggested that itopride hydrochloride has an inhibitory effect on I(Ca) at concentrations much higher than those in clinical use.
Morisawa
T
T
Department of Clinical Pharmacology, Faculty of Medicine, Tottori University, Yonago, Japan.
Hasegawa
J
J
Hama
R
R
Kitano
M
M
Kishimoto
Y
Y
Kawasaki
H
H
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001593:Benzyl Compounds / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D051668:Delayed Rectifier Potassium Channels; D004553:Electric Conductivity; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000166:cytology; D015221:Potassium Channels / Q000187:drug effects*; D024642:Potassium Channels, Voltage-Gated; D016276:Ventricular Function
D001549:Benzamides; D001593:Benzyl Compounds; D020746:Calcium Channels, L-Type; D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C102254:itopride