Disease relevance of bepridil

• Verapamil and bepridil failed to block the [Ca]i rise induced by anoxia and were equally ineffective on anoxic gene expression [1].
• This study suggests that bepridil, 400 mg daily, is effective for the treatment of exercise-induced myocardial ischemia and angina pectoris [2].
• CONCLUSION: Bepridil plasma concentrations needed in vitro to modulate MDR could be achieved in this study with tolerable toxicity; however, despite most tumors being MDR1/Pgp-positive, no response was obtained that could be attributed to the drug combination [3].
• PURPOSE: To achieve an adequate plasma concentration of bepridil, a calcium channel blocker, which reverts multidrug resistance (MDR) in vitro, when administered in combination with vinblastine in patients with advanced colorectal cancer, a tumor characterized by high MDR1 gene expression [3].
• In two patients with intranodal reciprocal rhythm, the injection of bepridil terminated the tachycardia which could not be reinitiated later [4].

High impact information on bepridil

• Trifluoperazine, bepridil, and cetiedil inhibited Ca2+-dependent 125I-CaM binding to erythrocyte membranes and CaM activation of membrane Ca2+-ATPase with IC50 values of approximately 12, approximately 17, and approximately 40 microM, respectively [5].
• In the present study, employing two unrelated Na+/Ca2+ exchange inhibitors, 3',4'-dichlorobenzamil (DCB) and bepridil, we investigated the role of NCX in platelet activation induced by various agonists in detail [6].
• 3',4'-Dichlorobenzamil (DCB) and bepridil, relatively specific inhibitors of Na+/Ca2+ exchanger, also inhibited the chymotrypsin-induced alpha IIb beta 3 activation, and the IC50 values of these inhibitors for fibrinogen binding were 25 mumol/L and 52 mumol/L, respectively [7].
• We found that calcium entry is both necessary and sufficient to induce axonal degeneration after axotomy, and may be inhibited by cobalt, manganese, dihydropyridines, and bepridil [8].
• Clinical and pharmacologic study of multidrug resistance reversal with vinblastine and bepridil [3].

Chemical compound and disease context of bepridil

• Direct pharmacological blockade of the Na+,Ca2+ exchanger during anoxia with bepridil or benzamil also significantly improved recovery [9].
• At dosages producing equivalent increases in atrioventricular nodal refractoriness, diltiazem and KB-944 failed to increase the electrical current threshold required to produce ventricular fibrillation, whereas bepridil elevated the fibrillation threshold from 4.2 +/- 0.5 mA predrug to 14.7 +/- 2.2 mA postdrug (P less than .01) [10].
• Comparative effects of nisoldipine, nifedipine and bepridil on experimental pulmonary hypertension [11].
• In the mouse chloroform-induced ventricular fibrillation model and in the guinea pig ouabain-induced arrhythmia model, drugs of classes I (amefalone, aprindine, lidocaine, mexiletine, phenytoin, procainamide, or quinidine), II (metoprolol or propranolol), and IV (bepridil) were active [12].
• TFP and bepridil also reduced the incidence of reperfusion-induced ventricular tachycardia whilst all 3 drugs reduced its duration [13].

Biological context of bepridil

• Moreover, platelet aggregation induced by various physiologic agonists was inhibited by DCB or bepridil, while platelet agglutination by ristocetin was not [7].
• Identification of binding sites for bepridil and trifluoperazine on cardiac troponin C [14].
• Treatment of confluent osteoblast cultures for 14 days with low levels of bepridil (3.0 microM) or KB-R7943 (1.0 microM and 0.1 microM) resulted in a significantly diminished capacity of these cells to mineralize bone matrix, without significantly altering cell morphology, viability, or cell differentiation [15].
• In group 2, heart rate (HR) and contractility initially increased (8% and 10%, respectively, P less than 0.05 vs C), secondary to the greater fall in afterload, followed by a significant reduction at 5 and 10 min after bepridil (9% and 10%, respectively), accompanied by a 36% increase in LV enddiastolic pressure (P less than 0.05 vs C) [16].
• Cardiac output, measured immediately after bepridil, was unaltered, although in group 2 stroke volume index increased (14%) and systemic resistance decreased (16%), both P less than 0.05 vs C [16].

Anatomical context of bepridil

• Inhibition of Na+/Ca2+ exchange with KB-R7943 or bepridil diminished mineral deposition by osteoblasts [15].
• Dose related coronary and systemic haemodynamic effects of intravenous bepridil in patients with coronary artery disease [16].
• Bepridil markedly increased the refractory period of the atrium, atrioventricular node and the AH-interval [4].
• Since bepridil protects the myocardium and minimises ischaemia induced damage these events might be related to a calmodulin antagonistic action as well as a calcium channel blocking action [17].
• The effect of the Pgp modulator bepridil on steady-state cellular daunorubicin (DNR) and vincristine (VCR) accumulation and chemosensitivity of these XG cells was compared with its effects in the cell lines (CL). mdr1 mRNA and Pgp (by flow cytometry) were measured [18].

Associations of bepridil with other chemical compounds

• IC50 values of bepridil and cetiedil for thyroid hormone response of the enzyme were 5 x 10(-5) and 2 x 10(-5) M, respectively, whereas IC50s of these agents for enzyme activity in the absence of thyroid hormone were both 10(-4) M [19].
• Similarly, there are multiple clinical and biological data suggesting that intracoronary nifedipine, diltiazem or bepridil, and intracoronary or intravenous nicardipine might result in a reduced incidence of myocardial ischaemia during PTCA [20].
• Digoxin and bepridil reduced heart rate and prolonged the PQ interval because of negative chronotropic and dromotropic properties [21].
• We examined the effects of the calcium channel blockers nitrendipine, diltiazem, verapamil, bepridil, and mibefradil on the cloned HERG and KvLQT1/IsK K+ channels [22].
• Verapamil protected target cells from lysis by amoebae (P less than 0.005), whereas bepridil reduced the capacity of amoebae to kill Chinese hamster ovary cells (P less than 0.001) [23].

Gene context of bepridil

• The antiarrhythmic KCNQ1 channel blocker bepridil inhibited KCNQ4 with an IC(50) value of 9.4 microM, whereas clofilium was without significant effect at 100 microM [24].
• Micromolar bepridil inhibited tail currents carried by KCNQ1/KCNE1 channels in a concentration-dependent manner (IC50 = 5.3 +/- 0.7 microM at -40 mV from 1000 milliseconds test pulse) [25].
• The effect of bepridil on DNR and VCR accumulation and chemosensitivity in the XG cells was in accordance with the XG expression of mdr1/Pgp [18].
• It is shown that bepridil blocks both cellular calcium entry as measured by Mn2+ quenching of fura-2 fluorescence and activation of the Na+/H(+)-exchanger following expression of the Ha-ras oncogene [26].
• 10 mumol/l bepridil inhibit oscillations of PD and protect +ras cells against actin stress fiber depolymerization [26].

Analytical, diagnostic and therapeutic context of bepridil

• Four patients experienced side effects that limited therapy (dizziness in three and abnormal results of liver function tests in one) and one patient died during the bepridil phase [2].
• Binding of a calcium sensitizer, bepridil, to cardiac troponin C. A fluorescence stopped-flow kinetic, circular dichroism, and proton nuclear magnetic resonance study [27].
• The influence of bepridil on steady-state serum digoxin concentrations (SDCs) and the pharmacodynamic actions of both drugs were tested in 48 healthy subjects in a randomized, double-blind study [21].
• Positive inotropism from digoxin shortened the corrected electromechanical systole (QS2c) and the preejection period and increased impedance cardiography [(dZ/dt)/RZ index]; the opposite effects occurred after bepridil, indicating negative inotropism [21].
• Pretreatment with bepridil for 5 min before ischemia improved the recovery of developed tension measured after 60 min of reperfusion [28].

References