STUDIES ON PHARMACOLOGIC ACTIONS OF LAPPACONITINE HYDROBROMIDE

Lappaconitin e was isolated from the root of Aconitum sinomantanum Nakai which has been used as an anodyne in the northwestern part of China. In this paper, the analgesic effects of lappaconitine were demonstrated by using the mice hot plate method and the rat tail-flick test after intraperitoneal injection of 6 mg/kg. Assayed with the writhing method, the median analgesic dose (ED₅₀) of lappaconitine in mice was found tO be 3.5 mg/kg. In the 2-day test⁽⁸⁾, no jumping was observed in mice treated with lappaconitine and then challenged with nalorphine. The single dose suppression test was applied to estimate addiction liability of lappaconitine in morphine-treated rats, the change in body weightwas not significantly different from that seen in the control after given lappaconitine at doses of 8 mg/kg. In three morphine-dependent monkeys, lappaconitine at doses of 2 mg/kg, which was the maximal tolerated dose, did not suppress the withdrawal symptoms evoked by sudden morphine withdrawal or by subcutaneous injection of nalorphine (0.5 mg/kg). In three monkeys, lappaconitine were administrated for 53-92 days, and the physical dependence was determined. During this period no physical dependence was observed. No withdrawal symptoms were observed when challenged with nalorphine at doses of 4-8 mg/kg.Anaesthesia test on rabbit cornea showed that the surface anaesthetic potency of lappaconitine was eight times stronger than that of cocaine. Its local anesthetic activities on sciatic nerve block in mice and intracutaneous wheal test in guinea pig were found to be 5 times and about the same, respectively, as active as cocaine.Iappaconitine was shown to have antithermic effect in normothermic and pyrexial mice after intraperitoneal injection of 3 mg/kg. In rats, after intraperitoneal injection lappaconitine 4 mg/kg qd × 7 days, a marked reduction in formaldehydeinduced edema of the hind paw was noted.