Bepridil for recurrent sustained ventricular tachycardias: Assessment using electrophysiologic testing

Lévy, Samuel; Cointe, R; Metge, M; Faugère, G; Valeix, B; Gérard, R

doi:10.1016/0002-9149(84)90252-2

Cited by 21 publications

(8 citation statements)

References 2 publications

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“…However, two early recurrences of VT were noted in these patients, and the real efficacy of this dosage of bepridil is 44%. Similar results were noted by Levy [3] and Fauchier [5]: With a dose of 600 mg/day, oral bepridil therapy prevented VT initiation in 6 out of 9 patients (66%). (Table 3) We compared responders to nonresponders with regard to clinical and electrophysiologic variables.…”

Section: Role Of Bepridil In Preventing Inducible Vtsupporting

confidence: 86%

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

Brembilla‐Perrot

Aliot

Clémenty³

et al. 1992

Cardiovasc Drug Ther

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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)

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Section: Role Of Bepridil In Preventing Inducible Vtsupporting

confidence: 86%

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

Brembilla‐Perrot

Aliot

Clémenty³

et al. 1992

Cardiovasc Drug Ther

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“…In this respect bepridil is unique. Such properties could account for the activity of bepridil against both supraventricular and ventricular arrhythmias (Fauchier et al, 1985;Levy et al, 1984;Rowland et al, 1985) in addition to its pronounced antianginal properties (Alpert et al, 1985). Comparison of bepridil with its quaternary ammonium derivative, CERM 11888, indicated that intracellular effects, in addition to an action upon slow calcium and fast sodium channels, may be responsible for this unique pharmacological profile of bepridil.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the common property of calcium antagonists to inhibit the slow calcium current, bepridil also inhibits sodium channels (Schwartz et al, 1985; Sperelakis, 1987). The combination of these two effects may explain its additional antiarrhythmic properties in animal experiments (Marshall et al, 1984;Flaim & Cummings, 1986) and its efficacy against both supraventricular (Rowland et al, 1985) and ventricular (Levy et al, 1984) arrhythmias in man. However, bepridil also enters cells (Sperelakis, 1987) and is able to modulate intracellular calcium movements, 1 Author for correspondence.…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological effects of bepridil and its quaternary derivative CERM 11888 in closed chest anaesthetized dogs: a comparison with verapamil and diltiazem

Leboeuf

Lamar

Massingham

et al. 1989

British J Pharmacology

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1 The electrophysiological effects of bepridil, its quaternary derivative, CERM 11888 (methylpyrrolidinium bromide) (both 2.5mgkg-1 i.v.) and those of verapamil and diltiazem (0.2mgkg-' i.v.) were studied in closed chest anaesthetized dogs at doses used in clinical studies. 2 The four drugs caused a bradycardia with the following order of potency: bepridil > CERM 11888 > diltiazem > verapamil. 3 All the compounds slowed conduction in the AV node, increased the refractory period (RP) and decreased Wenckebach rates with the following order: verapamil > diltiazem > bepridil > CERM 11888. 4 Verapamil and diltiazem did not affect conduction or the RP in atria while bepridil weakly slowed the former and markedly increased the latter. CERM 11888 caused a lengthening of RP but this was a delayed effect. 5 In the ventricle, bepridil and CERM 11888 caused a small increase in the QRS and a more pronounced increase in the RP. Both compounds increased QTc but did not modify HV. Verapamil and diltiazem had no significant effects at the ventricular level. 6 Our results confirm that the main sites of action of calcium antagonists are the SA and AV nodes. Bepridil has a broader spectrum of activity and also acts at the atrial and ventricular levels. A comparison of the effects of bepridil with those of its quaternary derivative suggests the involvement of an intracellular action in the electrophysiological effects of bepridil.

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“…Regarding ventricular arrhythmias bepridil was effective in non-responding VT in the dose of a single 800 mg followed by 500-600 mg as it prevented VT initiation in 66 % of the cases and caused side effects (paralytic ileus) in only 1 patient. Three patients remained symptom-free over a follow-up of 4 to 13 months [369]. Bepridil prevented VT induction in 47 % of patients with symptomatic VT [370].…”

Section: Human Data On Hemodynamic Effects Of Monatepilmentioning

confidence: 90%

“…) proved to possess antiarrhythmic properties using the epinephrine-, digitalis-and twostage coronary ligation-induced canine ventricular arrhythmia models as intravenous administration of AP-792 (0.3 or 1.0 mg/kg) effectively suppressed each of the ventricular arrhythmias and its antiarrhythmic action was slow in onset and long-lasting [390]. [193] Mibefradil / applied as co-medication caused TdP [347] Bepridil / 200-600 mg/day for 3 weeks in persistent AF patients VT, prolongation of QTc interval and TdP was observed [134] Bepridil / 200-600 mg/day for 3 weeks in patients with persistent AF, induced VT, prolongation of QTc interval and TdP more often compared to amiodarone [134] Bepridil / 100-200 mg/day induced QT prolongation, bradycardia, TdP usually triggered by hypokalemia, sudden decrease in HR in patients with AF or AFL [386] Bepridil / plasma level of approximately 300 ng/ml suppressed AF [376] Bepridil / 100-200 mg/day successfully converted AF to SR in about half of the patients [377] [378] Bepridil / 150 mg/day for 2 weeks followed by 100 or 200 mg/day converted AF to SR in shorter time and maintained SR for a longer period compared to amiodarone [380] Bepridil / applied as co-medication with various antiarrhythmic drugs prevented paroxysmal AF, converted AF to SR in persistent AF [381] [382] [383] Bepridil / a single dose of 800 mg followed by 500-600 mg prevented VT initiation in nonresponding VT patients [369] Bepridil / 2 mg/kg intravenously terminated AV reentrant tachycardia in a third of patients [232] Bepridil / 900 mg/day prevented the induction of sustained VT in 50 % of patients [372] Bepridil / mean dose of 156 mg/day suppressed ventricular tachyarrhythmias and decreased the frequency of ventricular tachyarrhythmia recurrences in 30 % of the patients [373] Bepridil / 200 mg/day reduced the frequency of VF episodes in idiopathic VF [374] Bepridil / 900 mg for 2 days followed by 400 mg/day moderate antiarrhythmic efficacy in patients with ventricular arrhythmias…”

Section: Ap-792mentioning

confidence: 99%

Class IV Antiarrhythmic Agents: New Compounds Using an Old Strategy

Szentandrássy

Nagy²,

Hegyi³

et al. 2014

CPD

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Cardiac arrhythmias are a major cause of morbidity and mortality in the industrialized world. Among their treatment regimens one can find the calcium channel antagonists (CCAs), the class IV agents. In the cardiovascular system Land T-type calcium channels are found on vascular smooth muscle cells and cardiac myocytes with well defined physiological roles. Inhibition of calcium channels by CCAs has widely been used in clinical practice for several decades. Cardiovascular disorders are one of the many fields of medicine in which CCAs are used for various reasons and conditions. The three main indications of them are hypertension, angina and various cardiac arrhythmias. The most important classes of CCAs are dihydropyridines, phenylalkylamines and benzothiazepines but some newer compounds do not fall into any of these major classes. Dihydropyridines are not used in the antiarrhythmic therapy but are good vasodilators and antianginal agents. In contrast, phenylalkylamines and benzothiazepines exert cardiac actions in vivo and therefore these are one choice of antiarrhythmic drugs. This review focuses on phenylalkylamines, benzothiazepines and on new drugs with potential antiarrhythmic action in the heart as well as the mechanisms how calcium channels antagonism can lead to an antiarrhythmic action.

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Bepridil for recurrent sustained ventricular tachycardias: Assessment using electrophysiologic testing

Cited by 21 publications

References 2 publications

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

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

Electrophysiological effects of bepridil and its quaternary derivative CERM 11888 in closed chest anaesthetized dogs: a comparison with verapamil and diltiazem

Class IV Antiarrhythmic Agents: New Compounds Using an Old Strategy

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