title: Gnaphaliin A and gnaphaliin B synergize the relaxant effect of salbutamol but not of ipratropium in guinea pig trachea.
abstract: OBJECTIVE
  This work was aimed to investigate the pharmacodynamic interactions between gnaphaliins A and B with ipratropium bromide (IBR) and salbutamol (SAL) using the guinea pig trachea model through application of the combination index (CI)-isobologram equation.
  
  
  METHODS
  The guinea pig trachea rings in isolated chamber with Krebs-Henseleit solution (37°C) were contracted with carbachol (3 μm), and then, concentration-relaxant effect curves were constructed for individual drugs and in combination at fixed constant ratios (1 : 1, 3 : 1 and 1 : 3). Median effect and combination index (CI)-isobologram equations were used for determining interactions.
  
  
  RESULTS
  Gnaphaliin A and gnaphaliin B showed clear synergistic interaction with salbutamol, reducing the dose of salbutamol more than sevenfolds to produce the same relaxant effect. However, the combination of either flavonoids with ipratropium bromide showed no interaction.
  
  
  CONCLUSIONS
  Applying the combination index-isobologram method, we determined that gnaphaliin A and gnaphaliin B have synergistic effect with salbutamol due probably to their inhibitory effect on phosphodiesterases to maintain high levels of cAMP in the tracheal smooth muscle. However, these compounds did not show any effect with ipratropium.
authors.affiliation: Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, México, Mexico.|Departamento de Ciencias Naturales, DCNI, Universidad Autónoma Metropolitana, Unidad Cuajimalpa, México, Mexico.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodríguez-Ramos
authors.affiliation: Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, México, Mexico.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Andrade-Moreno
authors.affiliation: Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, México, Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Alfaro-Romero
authors.affiliation: Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, México, Mexico.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Balderas-López
authors.affiliation: Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, México, Mexico.
authors.forename: Andrés
authors.initials: A
authors.lastname: Navarrete
mesh_terms: D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005419:Flavonoids / Q000494:pharmacology*; D006168:Guinea Pigs; D041743:Herb-Drug Interactions; D066298:In Vitro Techniques; D009241:Ipratropium / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects*
chemical_list: D001993:Bronchodilator Agents; D005419:Flavonoids; C542036:gnaphaliin A; C542037:gnaphaliin B; D009241:Ipratropium; D000420:Albuterol
keywords: asthma; combination index-isobologram equation; drug interactions; gnaphaliins; salbutamol