Pharmacological studies of lappaconitine. Analgesia produced by intracerebroventricular, intracisternal and intrathecal injections.

The antinociceptive effects of lappaconitine (LA) and morphine (MOR) when injected intracerebroventricularly (i.c.v.), intracisternally (i.cist.) or intrathecally (i.t.) were investigated in mice by use of the tail pinch, hot plate and acetic acid-induced writhing tests. In addition, the effects of naloxone (NLX) administered subcutaneously on the antinociceptive action of LA and MOR were studied. LA and MOR after i.c.v., i.cist. and i.t. injection produced dose-dependent antinociception. MOR was more potent in the tail pinch and acetic acid-induced writhing tests by i.t. injection than by i.c.v. or i.cist. injection, but the potency in the hot plate test was independent of the injection site. On the other hand, like MOR, LA was more potent after i.t. injection than after i.c.v. or i.cist. injection in the tail pinch and acetic acid-induced writhing test. Its antinociceptive action was less potent than that of MOR. The antinociceptive actions of MOR were antagonized by NLX (1 mg/kg, s.c.) in every test and injection site, whereas the antinociceptive actions of LA were not inhibited, except for the antinociception on the tail pinch test, which was partially antagonized by NLX. It is suggested that LA mainly produced an NLX-resistant antinociceptive effect at the spinal site.