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At least 19 recordsLinked to original sources
PubMed1985

Long-term efficacy of bepridil in patients with chronic stable angina pectoris: results of a multicenter, placebo-controlled study of extended bepridil use.

To evaluate whether bepridil once a day provides effective antianginal therapy during extended use, a placebo-controlled withdrawal study was conducted in 33 patients with chronic stable angina. Each patient studied had previously had a favorable response to short-term administration of bepridil and had been taking the drug once daily for greater than or equal to 9 months of continuous use. Patients were then randomly assigned to receive either continued bepridil or a placebo substitution once daily during a 4-week, double-blind, parallel-group comparison. Dosage for the bepridil group was constantly maintained for each patient at a level observed to be clinically effective. The study consisted of a comparison of angina frequency and nitroglycerin tablet consumption obtained from patient diaries and results from maximal-graded multistage treadmill tests. Patients randomized to continue receiving bepridil remained stable in terms of angina frequency and exercise performance. Discontinuation of long-term bepridil significantly increased angina frequency and nitroglycerin tablet consumption and reduced exercise capacity. Four patients (24%), all receiving placebo treatment, had increases in angina frequency and had the study terminated. Bepridil was reinstituted in these patients with resolution of symptoms and no untoward effects. The results of this placebo-controlled, double-blind, randomized study confirm that bepridil continues to provide antianginal benefit during long-term administration.

Adult↗
PubMed1991

Comparative efficacy and safety of bepridil and diltiazem in chronic stable angina pectoris refractory to diltiazem. The Bepridil Collaborative Study Group.

The efficacy and safety of bepridil hydrochloride (200 to 400 mg/day) were evaluated in patients with chronic stable angina refractory to maximal tolerated doses of diltiazem (median 360 mg/day) in a randomized, multicenter, double-blind, parallel study. Baseline diltiazem data were obtained during a 2-week period, after which 86 patients were randomized to bepridil (n = 46) or diltiazem (n = 40). Angina frequency, nitroglycerin consumption and ischemic manifestations induced by exercise treadmill testing were evaluated over 8 weeks. Bepridil significantly (p less than 0.05) increased time to angina onset, time to 1 and 2 mm of ST-segment depression, total exercise time and total work over baseline values. Changes in time to angina onset and time to 1 mm of ST-segment depression were significantly (p less than 0.05) greater for bepridil than for diltiazem. Angina frequency and nitroglycerin consumption did not differ significantly between groups. Compared with baseline, bepridil significantly (p less than 0.001) decreased heart rate (mean 4 beats/min) and prolonged QTc (mean 35 ms). The most frequent adverse effects in both groups were nausea, asthenia, dizziness, headache and diarrhea. Four patients taking bepridil and 1 taking diltiazem withdrew from the study because of adverse reactions. No sudden deaths, myocardial infarctions or instances of sustained ventricular tachycardia or torsades de pointes occurred in either group. The data indicate that bepridil provided safe and effective antianginal and antiischemic therapy in patients with chronic stable angina who exhibited less than optimal response to maximal tolerated doses of diltiazem.

Adult↗
PubMed1986

Effects of bepridil and diltiazem on [3H]nitrendipine binding to canine cardiac sarcolemma. Potentiation of pharmacological effects of nitrendipine by bepridil.

[3H]Nitrendipine binds to canine cardiac sarcolemma in a specific, saturable and rapid manner. Bepridil, a Ca++ channel inhibitor, stimulates this binding at submicromolar concentrations, but inhibits it noncompetitively at higher concentrations (IC50 = 15.8 microM). The increase in binding was due primarily to a 30% increase in the association rate constant (k+1) of [3H]nitrendipine, causing a decrease in the KD from a control value of 0.40 to 0.28 nM. In contrast to bepridil, diltiazem causes only an increase in [3H] nitrendipine binding without any inhibition. The increase was due primarily to an increase in receptor site density (maximum binding). These results show that the regulatory effects of bepridil and diltiazem on [3H]nitrendipine binding to cardiac tissue are different. The stimulatory effects of bepridil appeared to be pharmacologically relevant as low concentrations of bepridil potentiated the negative inotropic effect of nitrendipine in isolated perfused rat hearts.

Animals↗
PubMed1992

Evaluation of bepridil efficacy by electrophysiologic testing in patients with recurrent ventricular tachycardia: comparison of two regimens.

The purpose of the study was to evaluate this effect of different doses of intravenous and oral bepridil on the induction of ventricular tachycardia. Thirty-eight patients underwent electrophysiologic evaluation for recurrent ventricular tachycardia (VT). Sustained monomorphic VT was induced by programmed ventricular stimulation, using up to three extrastimuli in all patients. The effects of intravenous bepridil (2 mg/kg) were evaluated during the initial study. Intravenous bepridil prevented the induction of sustained VT in eight patients (21%). Electrophysiologic study was repeated after oral bepridil. In six patients the study was stopped because of adverse effects or VT recurrence. Thirty-two patients underwent repeat study 7 days later, taking oral bepridil, 500 mg/day (n = 16) or 900/day (n = 16). A dose of 500 mg/day of bepridil prevented the induction of sustained VT in only one patient. A dose of 900 mg/day of bepridil prevented the induction of sustained VT in eight patients. There were no significant clinical adverse effects, except in one patient receiving intravenous bepridil. The response to intravenous bepridil did not predict the response to oral bepridil. The response to intravenous or oral bepridil was not related to the plasma level of bepridil but was related to a higher left ventricular ejection fraction. Eight patients (21%) in whom VTs were noninducible on oral bepridil were discharged on 300 mg/day of bepridil if their initial loading dose was 500 mg/day or on 600 mg/day if their initial loading dose was 900 mg/day. They remained free of VT during a follow-up of at least 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Effects of the calcium entry blocker bepridil on repolarizing and pacemaker currents in sheep cardiac Purkinje fibres.

(1) Effects of bepridil (0.3-100 mumol/l) on transmembrane currents which are active during the repolarization of the cardiac action potential were studied in sheep cardiac Purkinje fibres with the two-microelectrode voltage-clamp technique. Transmembrane currents were activated at a frequency of 0.03 Hz. (2) The initial inwardly rectifying current (iK1) was reduced by 1.8 mumol/l bepridil to 70% of the reference iK1-current in the absence of the drug. (3) An initial outward current, which is activated at positive membrane potentials (iinst) was depressed to 70% of reference by 14 mumol/l bepridil. (4) The time-dependent outward current (iK) was decreased by 1.8 mumol/l bepridil to 70% of its amplitude in the absence of bepridil. The biexponential time course of iK-current activation changed to be monoexponential with 100 mumol/l bepridil. The effect of bepridil on iK-current resulted in a shift of the activation curve of iK-current to more positive membrane potentials (10 mumol/l bepridil) and an additional decrease of driving force and/or conductance of the iK-channels with higher bepridil concentrations (100 mumol/l). (5) The transient outward current (ito) was completely blocked by 30 mumol/l bepridil. Inhibition to 70% of reference occurred with 1 mumol/l bepridil. The voltage-dependent inactivation of ito-current was affected by bepridil: the amplitude of the steady-state inactivation curve was reduced and ito-current was inactivated faster after application of bepridil. Bepridil caused no pronounced shift of the steady-state inactivation curve along the voltage axis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effects of bepridil and lidocaine on the intraventricular conduction in acutely ischaemic and infarcted canine myocardium.

Effects of bepridil, an antiarrhythmic and antianginal drug, on intraventricular conduction in acutely ischaemic and infarcted myocardium were examined in anaesthetized dogs, and compared with those of lidocaine. Bepridil at doses of 2 and 5 mg/kg markedly prolonged the conduction time of a premature excitation induced by a ventricular stimulation in the infarcted zone. The effect of bepridil was dependent on a coupling time of the stimulation. Bepridil showed a marked effect at a coupling time of 150 ms, while it showed no significant effect at a prolonged coupling time of 1 s. In other words, the effect of bepridil was interval-dependent. Lidocaine showed a similar interval-dependent effect, but the effect of lidocaine at a longer coupling time was less than that of bepridil. The premature stimulation produced severely delayed conduction which resulted in reentrant beats. Bepridil blocked these conductions, thereby preventing reentrant beats. In contrast to the depressant effect of bepridil in the infarcted myocardium, bepridil prevented the prolongation of conduction time during acute ischaemia. The alternation of the ST-T complex during acute ischaemia which is also an important arrhythmogenic factor was also attenuated by bepridil. Contrary to bepridil, lidocaine significantly enhanced the conduction delay and the alternation in the ST-T complex. In conclusion, bepridil as well as lidocaine showed an interval-dependent depression of the conduction in the infarcted zone of the heart, whereas during acute ischaemia bepridil in contrast to lidocaine attenuated the conduction delay and ST-T alternans.

Animals↗
PubMed1986

Effect of methylated bepridil on slow action potentials in cardiac muscle and vascular smooth muscle.

The anti-anginal agent bepridil blocks slow Ca2+ channels in a variety of tissues. Since bepridil accumulates inside cells, the possibility exists that bepridil acts, at least partially, from inside the cell. To test this possibility, we examined the effects of a quaternary ammonium analog of bepridil, methylated bepridil, which presumably would enter the cells less readily, on the Ca2+-dependent slow action potentials of guinea pig papillary muscles (in 25 mM [K+]0) and rabbit pulmonary arteries (in tetraethylammonium chloride). In cardiac muscle, methylated bepridil had little effect on the slow action potentials at low stimulation frequencies (0.5 Hz), but at higher frequencies (1.0 and 2.0 Hz) the slow action potentials were depressed and/or the muscle was unable to follow each stimulation. These effects are similar to those obtained with bepridil, but bepridil was more potent than methylated bepridil. In vascular smooth muscle cells, methylated bepridil inhibited the slow action potentials at a somewhat lower dose than bepridil. We conclude that, in cardiac muscle, bepridil probably has two sites of action, one outside the cell (presumably on or associated with the slow Ca2+ channel) and a second site inside the cell. On the other hand, in vascular smooth muscle cells, bepridil may act only on an external site.

Action Potentials↗
PubMed1995

Effects of hemodialysis on plasma protein binding of bepridil.

The effects of end-stage renal disease (ESRD) and hemodialysis on the in vitro plasma protein binding of bepridil hydrochloride were investigated. The possible influence of bepridil metabolites on bepridil-protein binding in ESRD patients was also examined. Plasma samples were obtained from six patients with ESRD. Bepridil-plasma protein binding was measured by microequilibrium dialysis after addition of freshly prepared bepridil-14C (239 microCi/mg) at a final concentration of 2 micrograms/mL. The percentage of free bepridil in peripheral venous samples drawn on a nondialysis day was lower (i.e., binding was greater) in the patients with ESRD relative to previous observations in healthy subjects (0.15% +/- 0.04% versus 0.31% +/- 0.05% (mean +/- SD). The plasma concentrations of alpha-1-acid glycoprotein (AAG), the principal bepridil binding protein, were also higher in ESRD patients (110 +/- 32 mg/dL) than previously reported in healthy subjects. Although hemodialysis resulted in significant increases in AAG, total protein, and albumin concentrations, no significant difference in bepridil-plasma protein binding was detected between predialysis and postdialysis peripheral venous samples in the presence (0.16 versus 0.18) or absence (0.20 versus 0.17) of bepridil metabolites. The percentage of free bepridil in plasma from both the arterial and venous limbs of the dialyzer during hemodialysis (means of free bepridil ranged from 0.24-0.28%) was higher than in samples drawn from a peripheral vein. This displacement of bepridil from its binding sites as blood passes through the dialyzer may have been owing to the presence of high local concentrations of plasticizers. Confirmation of this hypothesis will require further investigation.

Adult↗
PubMed1987

Comparison of bepridil with nadolol for angina pectoris.

Bepridil hydrochloride is a unique calcium channel-blocking drug with anti-ischemic and type 1 antiarrhythmic properties. With a half-life of more than 40 hours, once-daily therapy is possible. Twenty-four patients (22 men, 2 women), mean age 58 years (range 43 to 72), with stable exertional angina were assigned to therapy with bepridil and nadolol in a randomized, double-blind, crossover trial. Antianginal efficacy was assessed by a diary of angina frequency and nitroglycerin consumption as well as by treadmill exercise testing. The effect of therapy on ventricular function was assessed by symptom-limited equilibrium gated exercise radionuclide angiography. During therapy with both nadolol and bepridil, the number of episodes of angina per week was significantly reduced and nitroglycerin consumption decreased compared with baseline evaluation. Exercise duration was prolonged by both therapies (baseline 281 +/- 122 seconds, nadolol 377 +/- 96 seconds, bepridil 400 +/- 109 seconds; p less than 0.005 for nadolol and bepridil vs baseline). Time to the onset of angina was similarly prolonged, 50% by nadolol and 65% by bepridil (p less than 0.005). Bepridil had no effect on PR and QRS durations, although QTc was significantly prolonged (baseline 0.43 +/- 0.03, nadolol 0.42 +/- 0.03, bepridil 0.45 +/- 0.04; p less than 0.005 for bepridil vs baseline and nadolol). By radionuclide angiography, neither nadolol nor bepridil had an adverse effect on left ventricular function at rest or during exercise. Bepridil therefore provides effective therapy for angina without adverse effects on left ventricular function, comparable to the effects of beta blockade with nadolol.

Adult↗
PubMed1992

Comparative efficacy of bepridil versus placebo in angina pectoris: treatment and withdrawal studies.

The efficacy and safety of once-daily doses of 200, 300, and 400 mg of bepridil hydrochloride were compared with placebo in a 14-week multi-center, double-blind parallel study. All doses of bepridil significantly reduced weekly anginal attacks and nitroglycerin consumption from baseline levels. Bepridil also significantly improved total exercise time, time to angina, time to 1 mm ST-segment depression, and total work. Reduction in heart rate (maximum mean decreases of 7-8 beats/min) and prolongation of QT and corrected QT (QTc) intervals were associated with bepridil therapy. Bepridil was well tolerated; most adverse reactions reported were mild and tolerable even at the 400-mg dose. This study provides strong support for the use of bepridil in patients with chronic stable angina pectoris that is not optimally controlled by other available antianginal therapies. A double-blind withdrawal study is also reported, in which patients stabilized on bepridil were randomized to either continue on bepridil therapy or receive placebo. Patients who were withdrawn from bepridil therapy showed significant increases in the number of weekly anginal attacks and nitroglycerin consumption compared with levels seen during long-term treatment. Patients withdrawn from bepridil therapy showed significant deterioration in exercise tolerance compared with baseline and with those maintained on bepridil.

Adult↗
PubMed1987

Bepridil: a new long-acting calcium channel blocking agent.

Bepridil is an investigational calcium channel blocking agent with antianginal activity that has a distinct and complex pharmacologic profile. Bepridil produces significant coronary vasodilation and modest peripheral effects, in addition to negative inotropic and chronotropic effects. Bepridil favorably modifies both myocardial oxygen demand and supply, supporting its use as an antianginal drug. Electrophysiologically, bepridil exhibits classes I, III, and IV antiarrhythmic activity. Five U.S. trials evaluating the short-term antianginal efficacy of bepridil collectively reported that bepridil causes significant improvement in both subjective and objective parameters of efficacy without depressing left ventricular function. In addition, one U.S. trial reported continued antianginal effects of bepridil after long-term use. There are limited data comparing and/or combining bepridil with other antianginal drugs, but the available information is promising. Limited information also exists on the use of bepridil in acute myocardial infarction and arrhythmias. Tolerance to bepridil therapy has been excellent, with the most common adverse effects being diarrhea and dizziness. It is unclear whether bepridil will be used as a first-line agent in the treatment of chronic stable angina pectoris; however, its long half-life, which makes once daily dosing possible, is certainly a significant advantage.

Angina Pectoris↗
PubMed1992

Bepridil. A review of its pharmacological properties and therapeutic use in stable angina pectoris.

Bepridil is a calcium antagonist with direct negative chronotropic, dromotropic, inotropic and vasodilatory actions which reduces myocardial oxygen consumption and increases coronary blood flow, leading to a significant anti-ischaemic and antianginal effect in the absence of reflex tachycardia. In contrast to other calcium channel blockers, bepridil produces only modest peripheral vasodilatation and displays weak antihypertensive activity. Its plasma elimination half-life of 1 to 2 days permits once daily administration. Results of short term clinical trials have shown bepridil to be of comparable efficacy to nifedipine, verapamil, diltiazem, propranolol and nadolol in decreasing the frequency of anginal attacks and consumption of nitroglycerin (glyceryl trinitrate) in patients with stable angina. Bepridil is more effective than nifedipine in improving exercise performance in patients with stable angina. Although bepridil proved superior to diltiazem in improving exercise performance in patients refractory to diltiazem, further studies are required to confirm the efficacy of bepridil in patients refractory to, or intolerant of, other antianginal agents. Bepridil in therapeutic doses is well tolerated, and appears to have a similar adverse effect profile to the established calcium antagonists. However, rate-dependent prolongation of the QTc interval and development of torsade de pointes have been associated with the use of bepridil. Therefore, bepridil is contraindicated in patients with hypokalaemia, those receiving other drugs that may prolong the QT interval, and those with congenital QT interval prolongation. Future clinical research will help to further define the position of bepridil as an antianginal treatment relative to the traditional calcium antagonists; in the interim, bepridil is indicated for the treatment of patients with angina refractory to or intolerant of other agents.

Angina Pectoris↗
PubMed1994

[Comparative study of the efficacy and tolerability of bepridil and diltiazem in unstable angina. 277 patients].

Bepridil has been used only rarely in unstable angina since its long half-life could imply a delayed action. A loading dose could deal with this disadvantage. In order to confirm this hypothesis, a randomised trial was undertaken involving a 5 day comparison of bepridil at the dose of 300 mg/day after a loading dose (900 mg on D1, 500 mg on D2 and D3) with diltiazem 360 mg/day in 277 patients: 210 men and 67 women, with a mean age of 62.1 +/- 9.5, suffering from unstable angina confirmed by an ECG during symptomatic events showing reversible ST depression. A continuous 72 hour ECG record was obtained in 82 patients. Because of 69 inclusion errors, only 208 patients provided evaluable data (110 with bepridil and 98 with diltiazem), including 55 with continuous ECGs. Mortality (4.5% bepridil v. 3.1% diltiazem) and premature treatment terminations for therapeutic inefficacy (4.5% bepridil v. 7.1% diltiazem), myocardial infarction (3.6% bepridil v. 3% diltiazem), adverse events (3.6% bepridil v. 3% diltiazem) or at the patient's request (0.9% bepridil) were similar between the 2 groups. Efficacy regarding angina was similar, with 18.2% recurrences with bepridil and 21.4% with diltiazem during the first 72 hours, persisting without any difference beyond 72 hours. Resulting treatment adjustments concerning nitrates were identical in the 2 groups. Among the 55 patients with an evaluable continuous ECG (27 bepridil and 28 diltiazem, NS), 18 had recurrent ischemic episodes (9 bepridil and 9 diltiazem), 72.2% of which were clinically silent. Their total number, total duration and maximum amplitude of ST depression were similar in the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Bepridil as an antisickling agent: membrane internalization and cell rigidity.

The calcium channel antagonist, bepridil, beta-(2-methylpropoxy)methyl-N-phenyl-N-(phenylmethyl)-1-pyrrol idineethanamine monochloride monohydrate, inhibits the sickling of deoxygenated sickle (SS) erythrocytes, as determined by light microscopy. The anti-sickling effect was seen only in dilute suspensions of red cells. In concentrated erythrocyte suspensions, sickling was not inhibited and measurements of hematocrit and cell density were unchanged by bepridil. The determination of cell volume in dilute suspensions was complicated by bepridil's tendency to aggregate, but rapid measurements by electronic sizing also indicated no increase in cell volume, up to a bepridil concentration of 200 microM. Ektacytometry of dilute sickle cell suspensions suggested an explanation for the anti-sickling action of bepridil. Osmotic scan ektacytometry disclosed that bepridil initially increased the surface area of the red cell, as shown by a shift in the low osmolality minimum. This change was complete in 10 sec, the shortest time that could be measured. Subsequently, at concentrations that were observed to inhibit the sickling of deoxygenated sickle cells (100 microM or greater), red cells underwent a loss in surface area that was complete in 1 min. There was a concomitant loss of cell deformability. Light and scanning electron microscopy has previously shown that bepridil is a stomatocytic agent. Using transmission electron microscopy, we verified that the loss of surface area was a consequence of endocytosis, presumably as the end stage of the stomatocytic transformation induced by bepridil. Bepridil did not inhibit intracellular hemoglobin S polymerization even at 200 microM, as shown by oxygen scan ektacytometry. Bepridil thus appears to inhibit the sickling of deoxygenated SS cells by inducing endocytosis and lowering cell deformability. This mechanism may explain the anti-sickling effect of other basic amphiphiles, such as chlorpromazine.

Anemia, Sickle Cell↗
PubMedDate not supplied

Plasma protein binding of bepridil.

The binding of the calcium-channel blocking agent, bepridil HCl (Vascor), to plasma proteins was investigated using radiolabeled bepridil and equilibrium dialysis. Greater than 99.7% of added bepridil-14C was found to freshly collected human plasma. The binding was characterized by a saturable high-affinity site (KD = 32 ng/mL = 87 nM) on alpha1-acid glycoprotein (AAG) or on an AAG-human serum albumin complex and lower affinity binding sites on albumin and other plasma macromolecules. Bepridil that is not bound to plasma proteins is extensively distributed into erythrocytes as evidenced by a red blood cell to free drug distribution coefficient of 71 +/- 7. Despite this high value, the blood to plasma ratio of bepridil averaged only 0.67 in humans, indicating that most of the circulating drug is bound to plasma proteins. Bepridil protein binding was not affected by additions of nonesterified fatty acids. Free fractions of bepridil were enhanced by addition of verapamil, nifedipine, diltiazem, disopyramide, and warfarin but only at concentrations above those achieved clinically. Bepridil was also displaced by the plasticizer, tris-(2-butoxyethyl)phosphate. Plasma obtained from a small number of angina patients prior to bepridil administration showed no differences in ability to bind bepridil compared with plasma obtained from healthy subjects.

Angina Pectoris↗
PubMed1985

Pharmacokinetics and metabolism of bepridil.

Bepridil hydrochloride differs from the other calcium antagonists in structure as well as in several clinical pharmacokinetic characteristics. The drug is completely absorbed from the gastrointestinal tract, but first-pass extraction reduces oral bioavailability to approximately 60%. After single-dose administration, the elimination half-life of bepridil averages 33 +/- 15 hours. However, upon multiple dosing, a half-life of 42 +/- 12 hours is found. As with verapamil and diltiazem, bepridil clearance is decreased after multiple dosing. Bepridil is completely metabolized, presumably by hepatic oxidative processes. A total of 17 metabolites have been identified, but the contribution of any of these metabolites to observed clinical response is currently unclear. The free fraction of bepridil in plasma is low, averaging only 0.23%. Despite this high protein binding, in vitro studies indicate that the potential for drug-to-drug interactions based on displacement of bepridil from its binding sites is low. Bepridil follows a linear dose/plasma concentration relation after single and multiple doses of the drug in both healthy volunteers and patients with angina. However, mean steady-state plasma bepridil concentrations are higher in patients, indicating a greater average decreased clearance. Food does not interfere with bepridil absorption. At this time, no significant pharmacokinetic interactions between bepridil and digoxin have been detected.

Animals↗
PubMed1985

Evaluation of bepridil for the treatment of angina pectoris: evidence for preservation of left ventricular function.

The efficacy of bepridil (400 mg once a day) was assessed in 15 patients with exertional angina pectoris. All 15 patients reported substantial clinical improvement during bepridil treatment compared with placebo treatment. Episodes of angina were 11.8 +/- 4.1 (mean +/- standard error of the mean)/week with placebo and 3.8 +/- 1.6 with bepridil (p less than 0.05); nitroglycerin use was 9.1 +/- 3.3 tablets/week with placebo and 3.5 +/- 1.7 with bepridil (p less than 0.05). Five of 15 patients receiving bepridil did not experience angina during treadmill exercise; in the remaining 10 patients, time to onset of angina during exercise was 5.7 +/- 0.9 minutes with bepridil as opposed to 4.5 +/- 0.8 minutes with placebo (p less than 0.05). Left ventricular (LV) performance at peak exercise as measured by first-pass radionuclide angiography revealed the ejection fraction to be 38 +/- 3% during placebo therapy and 47 +/- 4% during bepridil therapy (p less than 0.0025). End-diastolic LV volume was unchanged, but end-systolic volume was 136 +/- 11 and 117 +/- 13 ml (p less than 0.05) and stroke volume was 82 +/- 6 and 97 +/- 9 ml (p less than 0.05) during placebo and bepridil therapy, respectively. Heart rate at peak exercise was 136 +/- 3 beats/min with placebo and 128 +/- 3 beats/min with bepridil; however, blood pressure was unchanged. These studies demonstrate that bepridil results in significant clinical improvement and enhanced LV performance in patients with angina pectoris.

Angina Pectoris↗
PubMed1985

Electrophysiologic and antiarrhythmic properties of bepridil.

Bepridil has been shown to block both slow- and fast-channel activity in the heart. Electrophysiologic studies in man demonstrate that oral and intravenous bepridil prolongs sinus cycle length, PR interval and QT interval, without apparently changing the QRS interval. In addition, the drug depresses atrioventricular (AV) nodal conduction, resulting in an increased AH interval. Refractoriness in the AV node, atrium and ventricle is increased. There is usually little or no change in the HV interval. The antiarrhythmic properties of bepridil have been noted in patients with supraventricular tachycardia, ventricular premature complexes (VPCs) and sustained ventricular tachycardia (VT). In 17 patients, intravenous bepridil was compared with either verapamil or ajmaline. AV nodal reentrant tachycardia was terminated in all patients with bepridil and verapamil. However, ajmaline was somewhat more effective than bepridil in patients with AV reentry (8 of 8 versus 5 of 8). In 12 of these 17 patients, oral bepridil (500 mg/day for 3 days) suppressed the induction of tachycardia or slowed its rate. In 3 studies of oral bepridil for VPCs, the drug was effective in 68%, 69% and 70% of patients. Another group of studies evaluated bepridil in a total of 30 patients with sustained VT. Intravenous bepridil terminated VT in 17 of 26 patients. The induction of VT by programmed ventricular stimulation was also prevented in 7 of 17 patients. Although torsade de pointes has been reported, its incidence appears to be low.

Ajmaline↗