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.