Gnaphaliin A and gnaphaliin B synergize the relaxant effect of salbutamol but not of ipratropium in guinea pig trachea.

ObjectiveThis 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. MethodsThe guinea pig trachea rings in isolated chamber with Krebs-Henseleit solution (37 degrees C) were contracted with carbachol (3m), 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. Key findingsGnaphaliin 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. ConclusionsApplying 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.