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Pharmacological studies on lappaconitine: possible interaction with endogenous noradrenergic and serotonergic pathways to induce antinociception.

Authors
Type
Published Article
Journal
Japanese journal of pharmacology
Publication Date
Volume
58
Issue
3
Pages
251–257
Identifiers
PMID: 1513074
Source
Medline
License
Unknown

Abstract

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 beta-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 alpha-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 beta-adrenoceptors and 5-HT2 receptors in the brain and alpha-adrenoceptors and 5-HT1 receptors in the spinal cord.

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