Acute Toxicity of Higenamine in Mice

Higenamine is a potent cardiotonic benzylisoquinoline alkaloid, isolated from the root of Aconitum japonicum Thunb. (Ranunclaceae)(1, 2), and also from several other natural products (3-7). Aconitum has been used as a cardiotonic, diuretic, and analgesic in traditional Chinese medicine. It has been reported that higenamine possesses cardiac stimulation activity mediated by the activation of adenylcyclase and the subsequent elevation of cyclic AMP (8). Higenamine directly interacts with the adrenergic β1 and β2 receptors in vitro and exhibits both potent inotropic and chronotropic effects in animals and humans (9). It also strongly inhibits human dihydropteridine reductase (10). Intravenous infusion of higenamine to a small group of bradyarrhythmic patients has been reported (11). The root of Aconitum is believed to be a narrow therapeutic window herb in traditional Chinese medicine and higenamine may cause toxic effect in animals and humans. There are no toxicology reports on higenamine in the literature. This paper describes the acute toxicity of higenamine in mice.