Pharmacology of bepridil

Gill, Alan; Flaim, Stephen F.; Damiano, Bruce P.; Sit, Siu Po; Brannan, Melvin D.

doi:10.1016/0002-9149(92)90953-v

Cited by 52 publications

(30 citation statements)

References 25 publications

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“…In 2-dimensional isotropic excitable media, this curvature effect is expressed by Eq [1] (26). Our high-resolution optical mapping enabled analysis of centrifugal propagation in the vicinity of a stimulation site and revealed that there is a linear relationship with a negative slope between the κ and the LCV as expected from Eq [1].…”

Section: Effects Of Bepridil On the Intercellular Electrical Couplingmentioning

confidence: 53%

“…Bepridil has both antianginal and antiarrhythmic effects (1). Clinical evidence suggests that bepridil is effective in the treatment of ventricular tachyarrhythmias refractory to other antiarrhythmic drugs (2,3).…”

Section: Introductionmentioning

confidence: 99%

“…The inhibitory action against K + and Ca 2+ channels are, by and large, more potent than that against Na + channels (6, 7). As to the intracellular events, bepridil inhibits calmodulin-dependent processes, for example, myosin light-chain kinase phosphorylation required for vascular smooth muscle contraction (1,16). The Ca 2+ affinity of cardiac troponin C is increased by bepridil (17).…”

Section: Introductionmentioning

confidence: 99%

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Bepridil Facilitates Early Termination of Spiral-Wave Reentry in Two-Dimensional Cardiac Muscle Through an Increase of Intercellular Electrical Coupling

et al. 2011

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Abstract.Bepridil is effective for conversion of atrial fibrillation to sinus rhythm and in the treatment of drug-refractory ventricular tachyarrhythmias. We investigated the effects of bepridil on electrophysiological properties and spiral-wave (SW) reentry in a 2-dimensional ventricular muscle layer of isolated rabbit hearts by optical mapping. Ventricular tachycardia (VT) induced in the presence of bepridil (1 μM) terminated earlier than in the control. Bepridil increased action potential duration (APD) by 5% -8% under constant pacing and significantly increased the space constant. There was a linear relationship between the wavefront curvature (κ) and local conduction . Dye transfer assay in cultured rat cardiomyocytes confirmed that bepridil increased intercellular coupling. SW reentry in the presence of bepridil was characterized by decremental conduction near the rotation center, prominent drift, and self-termination by collision with boundaries. These results indicate that bepridil causes an increase of intercellular coupling and a moderate APD prolongation, and this combination compromises wavefront propagation near the rotation center of SW reentry, leading to its drift and early termination.

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Section: Effects Of Bepridil On the Intercellular Electrical Couplingmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bepridil Facilitates Early Termination of Spiral-Wave Reentry in Two-Dimensional Cardiac Muscle Through an Increase of Intercellular Electrical Coupling

et al. 2011

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“…In electrophysiological studies, bepridil is a non-selective blocker of various ion channels similar to amiodarone; it inhibits I Na , I L-Ca , T-type Ca 2+ channels (I T-Ca ), I K , I K1 , transient outward K + channels (I to ), I KACh , I KNa , and hyperpolarization-activated non-selective cation channels (I f ) (23 -28). Bepridil acts also as a calmodulin antagonist and a Ca 2+ sensitizer (29). It has negative inotropic and chronotropic effects on the heart (30).…”

Section: Bepridilmentioning

confidence: 99%

Topics on the Na+/Ca2+ Exchanger: Pharmacological Characterization of Na+/Ca2+ Exchanger Inhibitors

2006

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Abstract. Using the whole-cell voltage clamp, we examined acute effects of various agents on Na + / Ca 2+ exchange current (I NCX ) in guinea-pig cardiac ventricular cells and transfected cells. Among the antiarrhythmic drugs, amiodarone, bepridil, dronedarone, cibenzoline, azimilide, and aprindine inhibited I NCX in a concentration-dependent manner. We also investigated the effects on NCX of 2,3-buanedione monoxim (BDM) and selective NCX inhibitors such as KB-R7943, SEA0400, and SN-6. The presence of trypsin in the pipette solution attenuated the inhibitory effects on NCX of amiodarone, bepridil, and BDM, suggesting that these drugs inhibit NCX from the cytosolic side. In contrast, the trypsin-insensitive NCX inhibitors were aprindine, azimilide, dronedarone, cibenzoline, KB-R7943, SEA0400, and SN-6. KB-R7943, SEA0400, and SN-6 suppressed the uni-directional outward I NCX more potently than the uni-directional inward I NCX . The mechanism of this mode-dependency is unknown, but is suggested to be related to intracellular Na + concentration.

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“…15 Bepridil produces a lidocaine-like fast kinetic block of the inward sodium current, blockade of several outward potassium currents and inhibition of sodium-calcium exchange. 15, 16 In Japan, bepridil is used as an antiarrhythmic drug because its unique electrophysiological properties make it behave like class I, class III and class IV antiarrhythmic drugs.…”

Section: 9 Bepridil and Outcome In Af Patientsmentioning

confidence: 99%

Clinical Outcome in Patients With Paroxysmal or Persistent Atrial Fibrillation Receiving Bepridil

Shiga

Suzuki

Naganuma

et al. 2011

Circ J

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Background: It is unknown whether bepridil improves cardiovascular events in atrial fibrillation (AF) patients, so this study evaluated the clinical outcome in paroxysmal or persistent AF patients receiving bepridil. Methods and Results:We conducted a cohort study of 284 consecutive patients who received bepridil for AF (25% female, 59±13 years) with a median follow-up period of 17 months (4-157 months). A total of 135 (48%) patients had structural heart disease, and 231 patients (81%) had previously received class I or class III antiarrhythmic drugs. The cumulative rates for cardiovascular events were 2.4%, 8.1%, and 10.1% at 1, 3, and 5 years, respectively. The cumulative rates for a composite of mortality, cerebral infarction, systemic embolism, major bleeding and heart failure were 9.7%, 18.2%, and 29.6% at 1, 3, and 5 years, respectively. The probability of progression to permanent AF was 23.5% at 5 years. Sudden death occurred in a patient with a prior myocardial infarction who was taking 200 mg daily, and torsade de pointes (Tdp) occurred in two patients without structural heart disease taking 200 mg daily. Excessive corrected QT interval prolongation (>0.50 s) was observed when plasma concentrations were higher than 800 ng/ml. Conclusions:Bepridil might not improve the clinical outcome in refractory AF patients. Bepridil-related adverse events, including QT prolongation and Tdp, occurred in a dose- and concentration-dependent manner. (Circ J 2011; 75: 1334 - 1342

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Pharmacology of bepridil

Cited by 52 publications

References 25 publications

Bepridil Facilitates Early Termination of Spiral-Wave Reentry in Two-Dimensional Cardiac Muscle Through an Increase of Intercellular Electrical Coupling

Bepridil Facilitates Early Termination of Spiral-Wave Reentry in Two-Dimensional Cardiac Muscle Through an Increase of Intercellular Electrical Coupling

Topics on the Na+/Ca2+ Exchanger: Pharmacological Characterization of Na+/Ca2+ Exchanger Inhibitors

Clinical Outcome in Patients With Paroxysmal or Persistent Atrial Fibrillation Receiving Bepridil

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