title: Determination of pharmacological interactions of uliginosin B, a natural phloroglucinol derivative, with amitriptyline, clonidine and morphine by isobolographic analysis.
abstract: Uliginosin B is a natural phloroglucinol derivative, obtained from Hypericum species native to South America. Previous studies have shown that uliginosin B presents antidepressant-like and antinociceptive effects. Although its mechanism of action is still not completely elucidated, it is known that it involves the activation of monoaminergic neurotransmission. The aim of the current study was to further investigate the antinociceptive mechanism of action of uliginosin B by combining it with different drugs used for treating pain in clinical practice. The intraperitoneal administration of uliginosin B, morphine, amitriptyline and clonidine, alone or in mixture, produced a dose-dependent antinociceptive effect in the hot-plate assay in mice. The effect of the mixtures of drugs was studied using an adapted isobologram analysis at the effect level of 50% of the maximal effect observed. The analysis showed that the interactions between uliginosin B and morphine was synergistic, while the interactions between uliginosin B and amitriptyline or clonidine were additive. These findings point to uliginosin B as a potential adjuvant for pain pharmacotherapy, especially for opioid analgesia.
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Eveline D
authors.initials: ED
authors.lastname: Stolz
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Liz G
authors.initials: LG
authors.lastname: Müller
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Camila B
authors.initials: CB
authors.lastname: Antonio
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Paola F
authors.initials: PF
authors.lastname: da Costa
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Gilsane L
authors.initials: GL
authors.lastname: von Poser
authors.affiliation: Laboratório de Farmacologia Bioquímica e Molecular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: François
authors.initials: F
authors.lastname: Noël
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. Electronic address: stela.rates@ufrgs.br.
authors.forename: Stela M K
authors.initials: SM
authors.lastname: Rates
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D020902:Hypericum / Q000737:chemistry; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D035261:Plant Components, Aerial / Q000737:chemistry
chemical_list: D000700:Analgesics; D000639:Amitriptyline; D009020:Morphine; D010696:Phloroglucinol; D003000:Clonidine; C547933:uliginosin B
keywords: Analgesia adjuvant; Curved isobologram; Morphine synergism; Phloroglucinol derivative; Uliginosin B