6-BENZOYLHETERATISINE - A CLASS-I ANTIARRHYTHMIC SUBSTANCE FROM ACONITUM-TANGUTICUM (MAXIM) STAPF

The antiarrhythmic action of 6-benzoylheteratisine (6-bh), a C-19 dite rpenoid alkaloid from Aconitum tanguticum (Maxim.) Stapf was investiga ted in left and right guinea pig isolated atria. Furthermore, possible effects on transmembrane action potential of isolated papillary muscl es were studied using microelectrode techniques. At concentrations of more than 6 x 10(-8) mol/l, preincubation with 6-bh suppressed arrhyth mias induced by aconitine, veratridine and ouabain. Bradycardia of the right atria as a sign of toxicity occurred at 1 x 10(-6) mol/l. The a lkaloid significantly reduced the maximum rate of rise of the action p otential as well as the action potential amplitude, indicating inhibit ion of voltage-dependent sodium channels as a functional principle. Ad ditionally, a use-dependent mode of drug-action could be demonstrated. We conclude therefore, that 6-bh is a naturally occurring class-I ant iarrhythmic substance. The compound is a main alkaloid of Aconitum tan guticum, a plant used to prepare a poison antidote in Chinese and Tibe tan folk medicine. It may be speculated that the poison antidote effec t is at least partially based on the antiarrhythmic properties of 6-bh .