title: Fangchinoline inhibited the antinociceptive effect of morphine in mice.
abstract: Fangchinoline (FAN), a non-specific calcium antagonist, is a major alkaloidal component of the creeper Stephania tetrandra S. Moore (or fenfangji). It has been shown to possess antagonistic activity on morphine-induced antinociception in mice. This study was undertaken to assess the antagonistic mechanism. The results demonstrated that FAN (IP) attenuated morphine (SC)-induced antinociception in a dose-dependent manner with significant effect at doses of 30 and 60mg/kg body wt. (IP) in the tail-flick test but not the tail-pinch tests, carried out in mice. This antagonism was abolished by pretreatment with a serotonin precursor, 5-hydroxytryptophan (5-HTP, IP), but not by pretreatment with a noradrenaline precursor, L-dihydroxyphenylalanine (L-DOPA, IP) in the tail-flick test. On the other hand, the development of morphine-induced analgesic tolerance was not prevented by FAN. These results suggest that the serotonergic pathway may be involved in the antagonism of morphine-induced antinociception by FAN and, in agreement with other reports, also indicates the possible dissociation of the morphine analgesic effect from its tolerance-development mechanism.
authors.affiliation: National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China.
authors.forename: L H
authors.initials: LH
authors.lastname: Fang
authors.forename: Y H
authors.initials: YH
authors.lastname: Zhang
authors.forename: B S
authors.initials: BS
authors.lastname: Ku
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D044182:Benzylisoquinolines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010147:Pain Measurement / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D018517:Plant Roots; D031609:Stephania tetrandra
chemical_list: D000470:Alkaloids; D044182:Benzylisoquinolines; D009292:Narcotic Antagonists; D010936:Plant Extracts; D009020:Morphine; C060802:fangchinoline