title: Synergistic interaction between diene valepotriates from Valeriana glechomifolia Meyer (Valerianaceae) and classical antidepressants: an isobolographic analysis.
abstract: OBJECTIVE
  Combinations of different classes of antidepressants (including herbal adjuvants) have been used as an alternative means of achieving better results in the treatment of depressed patients. However, studies characterizing the interactions between herbal adjuvants and antidepressants are lacking. This study is the first to investigate the interaction between diene valepotriates (VAL) from Valeriana glechomifolia, a species with antidepressant-like effects, and imipramine (IMI), desipramine (DESI) and bupropion (BUP). The interactions were assessed via isobolographic analyses, which represent a tool for evaluating interactions between drugs.
  
  
  METHODS
  The interaction between VAL and each antidepressant was evaluated in mice given concurrent oral administration of each drug with fixed ED50 ratios and subjected to a forced swimming test (FST). Spontaneous locomotion was measured in the open field test.
  
  
  RESULTS
  The drug combinations produced a dose-dependent anti-immobility effect in the FST without altering mouse locomotor activity. Isobolographic analysis revealed that VAL resulted in synergistic interactions in combination with each of the antidepressants tested.
  
  
  CONCLUSIONS
  The synergistic interactions between VAL and IMI, DESI and BUP highlight the potential for VAL to serve as adjuvants to antidepressant drugs and suggest that VAL does not directly target the same sites on neuronal transporters as the antidepressants.
authors.affiliation: Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, 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, Rio Grande do Sul, 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, Rio Grande do Sul, Brazil.
authors.forename: Andresa H
authors.initials: AH
authors.lastname: Betti
authors.affiliation: Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Vivian
authors.initials: V
authors.lastname: Herzfeldt
authors.affiliation: Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Stela M K
authors.identifier: http://orcid.org/0000-0001-7952-7830
authors.initials: SM
authors.lastname: Rates
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D016642:Bupropion / Q000494:pharmacology; D004357:Drug Synergism; D007099:Imipramine / Q000494:pharmacology; D039823:Iridoids / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D013550:Swimming / Q000502:physiology; D014632:Valerian / Q000737:chemistry*
chemical_list: D000928:Antidepressive Agents; D039823:Iridoids; C009643:valtrates (combination); D016642:Bupropion; D007099:Imipramine
keywords: Valeriana glechomifolia; antidepressant; isobolographic analysis; synergism; valepotriates