Analgesic effect and toxicity of 3,15-diacetylbenzoylaconine and comparison with its analogues

3, 15-Diacetylbenzoylaconine (Dia) is a new aconite alkaloid derivative. The analgesic ED50 (95% confidence limit) of sc Dia measured with the HAc-induced writhing method, hot-plate method and electric stimulation method in mice were 2.76 (2.34-3.26), 3.50 (2.69-4.54), and 4.20 (3.72-4.73) mg.kg-1, respectively. With the hot-plate method and tail flick method in rats, the analgesic ED50 of ip Dia were 2.75 (2.28-3.31) and 5.24 (4.35-6.31) mg.kg-1, respectively. The LD50 of sc Dia in mice and ip Dia in rats were 21.68 (17.25-27.25) and 10.96 (8.24-14.56) mg.kg-1, respectively. The magnitude of the analgesic therapeutic indices of Dia, 3-acetylaconitine (Ace) and aconitine (Aco) in all the above-mentioned algo-model were in the order of Dia > Ace > Aco. When they were injected iv at 0.1 ml.min-1 in rats, the doses of Dia, Ace, and Aco producing arrythmia were 3.3, 0.8, and 0.5 times as large as those producing analgesia while those of Dia, Ace, and Aco inducing respiratory inhibition were 3.9, 0.5 and 0.3 times, respectively. The magnitudes of the oil/water distribution coefficients with two method and the quotient ED50 icv/ED50 sc of Dia and Ace were > Aco.