[Effect of norepinephrinergic system on ipalbidine analgesia]

Ipalbidine (Ipa) is a photoactive alkaloid isolated from the seeds of ipomoea hardwickki Hemsl. The analgesic effects of Ipa were determined by rat tail flick method. A dose-dependent analgesic effect was found after s.c. or i.c.v. administration of Ipa, but no analgesia was observed after intrathecal injection, indicating that the analgesic effect of Ipa is central in origin, and it acts mainly on supraspinal substrate. The analgesic effect induced by Ipa (60 mg.kg-1, s.c.) was markedly reduced by reserpine (2 mg.kg-1, i.p.) given 24 h before Ipa, which was reversed by combined administration with i.c.v. norepinephrine (NE). In addition, Ipa-induced analgesia was significantly attenuated by electrolytic lesion of bilateral destruction of locus coeruleus, and combined administration with diethyldithiocarbamate (200 mg.kg-1, i.p.), phentolamine (10 mg.kg-1, i.p. or i.c.v.), and prazosin (3 mg.kg-1, s.c.). But no influence was observed on the analgesia of Ipa after administration of yohimbine (5 mg.kg-1, s.c.) or propranolol (10 mg.kg-1, i.p.). These results suggest that the analgesia caused by Ipa is closely related to the function of the central norepinephrinergic system, and probably mediated by indirectly acting on alpha 1 receptors, but not alpha 2 or beta receptors.