6-Benzoylheteratisine — a class-I antiarrhythmic substance from Aconitum tanguticum (Maxim.) Stapf

Abstract

The antiarrhythmic action of 6-benzoylheteratisine (6-bh), a C(19) diterpenoid alkaloid from Aconitum tanguticum (Maxim.) Stapf was investigated in left and right guinea pig isolated atria. Furthermore, possible effects on transmembrane action potential of isolated papillary muscles were studied using microelectrode techniques. At concentrations of more than 6 × 10(-8) mol/1, preincubation with 6-bh suppressed arrhythmias induced by aconitine, veratridine and ouabain. Bradycardia of the right atria as a sign of toxicity occurred at 1 × 10(-6) mol/1. The alkaloid significantly reduced the maximum rate of rise of the action potential as well as the action potential amplitude, indicating inhibition of voltage-dependent sodium channels as a functional principle. Additionally, a use-dependent mode of drug-action could be demonstrated. We conclude therefore, that 6-bh is a naturally occurring class-I antiarrhythmic substance. The compound is a main alkaloid of Aconitum tanguticum, a plant used to prepare a poison antidote in Chinese and Tibetan folk medicine. It may be speculated that the poison antidote effect is at least partially based on the antiarrhythmic properties of 6-bh.