Anti-arrhythmic activities of six indole derivatives of changrolin

The indole-derived compounds, which possessed side chains resembling those of changrolin (4-[3',5'-bis[(N-pyrrolidinyl)methyl]-4'-hydroxyaniline]-quinazoline) showed potent anti-arrhythmic activity by restoration of sinus rhythm from ouabain-induced tachycardia in guinea pigs. The potency was assessed by comparison of the maintenance time of sinus rhythm recovered from tachyarrhythmias induced by ouabain. The promising compound was MI2 with piperidyl residue on position 3 & 5 of phenol moiety. There was no difference in anti-arrhythmic activities resulting from substitutions between a benzene ring and methyl residue at position 2 of indole, but the latter had weaker parasympatholytic activity. The anti-arrhythmic activity of MI2 (greater than 60 min) was 2.4 times more potent then changrolin (25 min), but its anti-cholinergic activity was only half of the latter. To compare the suppressive effect on reperfusion-induced arrhythmias by iv MI2 at different time in relation to the ligation-reperfusion protocol, it was the most effective when administered either 30 min prior to coronary occlusion or at the moment of reperfusion. The compound MI might belong to the Ic group shown by the slowing impulse conduction within the heart.