aconitine and 2-n-propyl-3-dimethylamino-5-6-methylenedioxyindene

The 2-n-propyl- and 2-n-butyl-3-dimethylamino-5,6-methylenedioxyindene hydrochlorides are intracellular calcium antagonists with coronary dilating and antiarrhythmic effects against ouabain- and calcium-induced arrhythmias. In the present study, pretreatment with these tertiary methylenedioxyindenes afforded significant protection against the calcium-dependent arrhythmias induced by chloroform in mice. On the other hand, their antiarrhythmic activity against aconitine- and methacholine-induced arrhythmias in rats (in which calcium does not play a primary etiological role) was suggestive but not impressive. The quaternary derivative, 2-n-butyl-5,6-methylenedioxy-3-trimethylammonium iodide, which was synthesized with the expectation of being devoid of antiarrhythmic activity owing to its exclusion from the intracellular compartment, unexpectedly demonstrated greater antiarrhythmic potency than the tertiary analogues against calcium-induced arrhythmias in rats and chloroform-induced arrhythmias in mice. Like the tertiary methylenedioxyindenes, the protective activity of the quaternary analogue against arrhythmias induced by aconitine or by methacholine in rats was suggestive but not impressive. Because of the relative inactivity of the quaternary methylenedioxyindene in vitro, it is proposed that its in vivo activity may be due either to metabolic activation or to concentration in cardiac tissue in sufficient quantity to allow diffusion into cardiac cells down a concentration gradient or to alter membrane electrophysiological properties to the extent of exerting antiarrhythmic activity.

Topics: Aconitine; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Calcium; Calcium Channel Blockers; Chloroform; Indenes; Male; Methacholine Compounds; Rats; Rats, Inbred Strains