Investigations to characterize a new antiarrhythmic drug bisaramil.
Bisaramil is a new, orally active antiarrhythmic agent. We investigated and classified its mechanism of action according to Vaughan Williams [1]. We have found that bisaramil at the concentration range of 2-20 microM decreased the frequency and the force of the contraction in spontaneously beating guinea-pig's right auricle in a dose-dependent manner. Furthermore, bisaramil significantly prolonged the conduction time and effective refractory period both in the auricle and in the ventricle which were driven electrically. The atrioventricular conduction time, as measured on isolated rabbit heart preparation containing both auricles and the left ventricule, was also lengthened in the presence of bisaramil in a concentration-dependent manner. Bisaramil did not inhibit isoprenaline-induced tachycardia in anaesthetized cats, indicating that it has no beta-blocking activity. When tested on frog sciatic nerve, bisaramil showed a significant local-anaesthetic property well comparable to lignocaine (lidocaine). The drug caused a parallel shift of the dose-response curve to CaCl2 similar to that of the verapamil on isolated guinea-pig left auricle, indicating a possible Ca-antagonistic activity. The prolongation of the atrial, ventricular and atrioventricular conduction time as well as the lengthening of the effective refractory periods were also observed in anaesthetized dogs after an i.v. dose of 0.5 mg/kg bisaramil. On the other hand, this dose of bisaramil did not exert significant negative inotropic and unfavourable haemodynamic effect on anaesthetized dogs. In conclusion, bisaramil seems to be an effective antiarrhythmic drug having both class I (membrane stabilizer) and class IV (inhibitor of calcium transport) type activity.
Chemical Works of Gedeon Richter Ltd., Pharmacological Research Centre, Budapest, Hungary.
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D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001283:Atrioventricular Node / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002415:Cats; D004285:Dogs; D004558:Electric Stimulation; D004566:Electrodes; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011802:Quinidine / Q000494:pharmacology; D011817:Rabbits; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013268:Stimulation, Chemical
D000319:Adrenergic beta-Antagonists; D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D011802:Quinidine