Bepridil prolongs the action potential duration of guinea pig ventricular muscle only at rapid rates of stimulation

Comparison of Electropharmacological Effects of Bepridil and Sotalol in Halothane-Anesthetized Dogs

“…30,31 The negative inotropic action of bepridil was observed also after the high dose, which may be induced by its cardiac L-type Ca 2+ channel-blocking action and Na + channel inhibition. 5,32,33 The drug also decreased the heart rate and increased the sinus node recovery time after the high dose, which may be associated with its cardiac L-type, as well as T-type Ca 2+ channel-blocking actions 34,35 and inhibition of IKr. 6 In the dl-sotalol group, negative inotropic and chronotropic effects and hypotensive action were observed in addition to increased preload to the left ventricular, which were essentially in accordance with our previous study using -adrenoceptor blockers in the same animal model.…”

“…23,36,43 The results of bepridil are, generally, in accordance with a previous in vitro examination. 32 On the other hand, the pharmacological IKs blockade has been shown to enhance the reverse rate-dependent prolonging action of the IKr blocker, 44 yet the reason why bepridil lacks a rate-dependent profile cannot be fully explained by its IKr and IKs blocking effects. 6 In our previous study, the class Ia antiarrhythmic drug disopyramide and the class III antiarrhythmic drug amiodarone prolonged the MAP90 in a rate-independent fashion in doses that blocked Na + channels in the halothane-anesthetized canine model.…”

Repetitive Evaluation of Fibrillation Cycle Length Predicts the Efficacy of Bepridil for Interruption of Long-Lasting Persistent Atrial Fibrillation

“…[5][6][7] In accordance with these reports, the sodium channel blocking effect of bepridil is weak 15) and the blocking effects on the L-type calcium channel and potassium channels, namely, Ikr, Iks, and Ito, are stronger, 5,6,16) so bepridil is considered to act as a class III or class IV antiarrhythmic agent rather than a class I antiarrhythmic agent. 17) By considering the reentrant mechanism in the atrium, the cycle length should strongly depend on the conduction velocity in the fixed reentrant circuit, and the sodium channel blocking action will directly prolong the cycle length through a decrease in the conduction velocity.…”

Opposing Effects of Bepridil on Ventricular Repolarization in Humans Inhomogeneous Prolongation of the Action Potential Duration vs Flattening of Its Restitution Kinetics

“…[28][29][30] The APD prolongation using bepridil in guinea pig, unlike most of other class III drugs, 31,32 was not attenuated remarkably at high stimulation rates, suggesting minimal "reverse use-dependence". 28 Our observation in the human ventricle is concordant with the guinea pig result, because the prolongation of the MAPD90s in the bepridiltreated patients at the shortest and longest CLs tested (330 and 750 ms) was comparable (by 15.0 and 16.8% in the RVOT, and by 8.0 and 10.8% in the RVA compared with the controls). The present study also revealed that the prolongation of the MAPD50 by bepridil was appreciably less than that of the MAPD90, possibly reflecting the inhibition of ICa,L.…”