Pharmacological studies of lappaconitine. Occurrence of analgesic effect without opioid receptor.

The contribution of opioid receptor to lappaconitine (LA) induced analgesia was investigated by in vivo and in vitro methods. The antagonistic effects of naloxone (NLX) on the analgesic actions of LA (s.c.) and morphine (MOR, s.c.) were determined by the tail pressure method, the hot plate method and the acetic acid-induced writhing method in mice. The ED50 values of MOR in the absence of NLX were 3.82, 0.50 and 0.33 mg/kg, respectively, but in the presence of NLX, the analgesic effect of MOR was decreased and the ED50 values were changed to 41.6, 4.40 and 5.97 mg/kg, respectively. However, NLX did not affect the analgesic activity of LA. The ED50 values of LA in the three methods were 9.12, 3.34 and 1.70 mg/kg in the absence of NLX and 12.1, 4.19 and 2.88 mg/kg in the presence of NLX, respectively. The inhibitory effect of the LA on the electrically evoked contractions of isolated guinea-pig ileum was weaker than that of MOR, and differently from MOR, its effect was not antagonized by NLX. Additionally, LA did not abolish the electrically evoked contractions of isolated rabbit and mouse vas deferens. In conclusion, the results suggest that the opioid receptor was not involved in the analgesic activity of LA.