Interaction between terbutaline and ethyl 2-(4'-carboxybenzamido)-4-propionamidobenzoate sodium salt in tracheal smooth muscle relaxation of guinea pig.

Ethyl 2-(4-carboxybenzamido)-4-propionamidobenzoate sodium salt (AM-682) is a new, orally active, antiallergic compound which has been reported to inhibit the release of histamine and leukotrienes from mast cells more than disodium cromoglycate (DSCG) or Tranilast. In the present study, the interaction between terbulatine, a beta 2-receptor agonist, and AM-682 or met-A, AM-682's main metabolite in humans, in guinea pig tracheal smooth muscle was investigated by measuring the isometric tension in vitro. Combinations of terbutaline and AM-682 or met-A produced more than additive relaxant effects. Comparing the combined effects with the calculated algebraic sums of single drug effects, the differences were statistically significant for terbutaline 10(-9) mol/l and AM-682 3 X 10(-6) mol/l, 10(-5) mol/l and 3 X 10(-5) mol/l (p less than 0.01) or met-A 3 X 10(-6) mol/l, 10(-5) mol/l (p less than 0.05) on the spontaneous tone of tracheal smooth muscle, and for terbutaline 10(-9) mol/l and AM-682 10(-5) mol/l (p less than 0.01), 3 X 10(-5) mol/l (p less than 0.05) on the tension of tracheal smooth muscle induced by 5.4 X 10(-7) mol/l carbachol. Thus the tracheal smooth muscle relaxant effects of AM-682 and the beta 2-receptor agonist terbutaline were synergistic. It is suggested that the combination of AM-682 and a beta 2-receptor agonist, rather than administration of each drug separately, may provide the therapeutic advantage in the treatment of bronchial asthma.