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.