Studies on the bradycardia induced by bepridil

British Journal of Pharmacology
M BeaughardP Piris

Abstract

Bepridil, a novel active compound for prophylactic treatment of anginal attacks, induced persistent bradycardia and a non-specific anti-tachycardial effect, the mechanisms of which were investigated in vitro and in vivo. In vitro perfusion of bepridil in the life-support medium for isolated sino-atrial tissue from rabbit heart, caused a reduction in action potential (AP) spike frequency (recorded by KCl microelectrodes) starting at doses of 5 X 10(-6) M. This effect was dose-dependent up to concentrations of 5 X 10(-5) M, whereupon blockade of sinus activity set in. Bepridil at a dose of 5 X 10(-6) M, induced a concomitant reduction in AP amplitude (falling from 71 +/- 8 mV to 47 +/- 6 mV), maximum systolic depolarization velocity (phase 0) which fell from 1.85 +/- 0.35 V/s to 0.84 +/- 0.28 V/s, together with maximum diastolic depolarization velocity (phase 4) which fell from 38 +/- 3 mV/s to 24 +/- 5 mV/s. In vivo injection of bepridil at a dose of 5 mg/kg (i.v.) into 6 anaesthetized dogs which had undergone ablation of all the extrinsic cardiac afferent nerve supply, together with a bilateral medullo-adrenalectomy, caused a marked reduction in heart rate which fell from 98.7 +/- 4.2 beats/min to 76 +/- 5.3 beats/min sustained...Continue Reading

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Citations

Jul 18, 1989·European Journal of Pharmacology·E WinslowR J Marshall
Jun 1, 1991·Pacing and Clinical Electrophysiology : PACE·J Y Le HeuzeyJ Lekieffre
Jun 1, 1984·The American Journal of Cardiology·A SassineP Puech
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Jan 1, 1983·British Journal of Clinical Pharmacology·D P NichollsR G Shanks
Jan 1, 1984·British Journal of Pharmacology·T AnnoK Yamada
Apr 9, 1992·The American Journal of Cardiology·B N Singh
Apr 9, 1992·The American Journal of Cardiology·A GillM D Brannan
Jun 1, 1985·The American Journal of Cardiology·J W UpwardD E Jewitt

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