Analgesic action and no physical dependence of 3-acetylaconitine

The analgesic action of 3-acetylaconitine (AAc), an alkaloid isolated from Chinese herb Aconitum flavum, has been studied by the following methods; Mice writhing evoked by ip 0.7% acetic acid 10 ml/kg, mice licking hind paw on hot plate, continuous pain stimuli elicited by sc 2.5% formaldehyde 0.03 ml in fore paw of mice and rat tail-flick response to light irradiation. The relative potency of analgesic action of AAc was found to be 5.1-35.6 and 1250-3912 times that of morphin and aspirin, respectively. The analgesic action of AAc was not antagonized by naloxone, but was eliminated by ip reserpin 3 mg/kg 3 h prior to AAc. The results suggested that analgesic action of AAc may be related to the monoamine level in brain. Daily sc of AAc 0.25 mg/kg*9 d in mice with hot plate did not induce tolerance as seen with morphine. In nalorphine-challenged test, no jumping was seen in mice treated with AAc 3.35 mg/kg, the maximal tolerance dose. The single dose suppression test was applied to estimate addiction liability of AAc in morphine-treated rats, the change in body weight was not significantly different from that seen in the control after AAc 0.1 mg/kg. In 3 monkeys, AAc was injected sc bid for 92-95 d, no abstinence syndrome was seen after sudden AAc withdrawal or when challenged with nalorphine 4 mg/kg on d 21, 41, 52, 62, and 92, respectively. In 2 morphine-dependent monkeys, AAc did not suppress the abstinence syndrome evoked by sudden morphine withdrawal or by sc nalorphine 0.5 mg/kg. These results demonstrate that AAc belongs to the non-nacrotic analgesic.