Pharmacological Studies on Lappaconitine: Possible Interaction with Endogenous Noradrenergic and Serotonergic Pathways to Induce Antinociception

抄録

Systemic and intracerebroventricular (i.c.v.) injections of lappaconitine (LA) produced a dose-dependent inhibition of the response to thermal stimulation in sham-operated mice as assayed by the tail-immersion test. After spinal transection, the antinociceptive potencies of s.c.- or i.c.v.-administered LA were markedly reduced. Antinociception induced by systemically administered LA was clearly reduced by pretreatment with 6-hydroxydopamine or 5, 7-dihydroxytryptamine through the i.c.v. and intrathecal (i.t.) routes. When LA was administered by i.c.v.-injection, the LA-induced antinociception was reduced by pretreatment with timolol, a β-adrenergic antagonist, and ketanserin, a 5-HT₂ antagonist. Administration of LA by the i.t. route resulted in a significant antinociceptive activity, which was also reduced by pretreatment with phenoxybenzamine, an α-adrenergic antagonist, and mianserin, a 5-HT₁ antagonist. The results of these studies suggest that the central noradrenergic and serotonergic systems may be involved in the antinociception of systemically administered LA, and these pathways are mediated by β-adrenoceptors and 5-HT₂ receptors in the brain and α-adrenoceptors and 5-HT₁ receptors in the spinal cord.