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

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 ring...

Full description

Saved in:
Bibliographic Details
Published in:Journal of pharmacy and pharmacology 2016-04, Vol.68 (4), p.533-541
Main Authors: Rodríguez-Ramos, Fernando, Andrade-Moreno, Miguel Ángel, Alfaro-Romero, Alejandro, Balderas-López, José Luis, Navarrete, Andrés
Format: Article
Language:English
Subjects:
Albuterol - pharmacology
Animals
asthma
Bronchodilator Agents - pharmacology
combination index-isobologram equation
Dose-Response Relationship, Drug
drug interactions
Drug Synergism
Flavonoids - pharmacology
gnaphaliins
Guinea Pigs
Herb-Drug Interactions
In Vitro Techniques
Ipratropium - pharmacology
Male
Muscle Relaxation - drug effects
Muscle, Smooth - drug effects
salbutamol
Trachea - drug effects
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Key findings 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.
ISSN:0022-3573
2042-7158
DOI:10.1111/jphp.12536