s-145 and ramatroban

Lung tissues produce a large amount of Thromboxane (Tx) A2. In addition to platelet aggregation and artery smooth muscle contraction, TxA2 strongly induces airway smooth muscle contraction and bronchial hyperresponsiveness. Not only TxA2, but many arachidonate cyclooxygenase metabolites such as PGD2, PGF2 alpha, PGH2, and others stimulate TP (PGH2/TxA2) receptor and can take a pathophysiological role for bronchial asthma. Several compounds competitively antagonizing TP receptor have been developed and being proved to have beneficial effects for treating of bronchial asthma in clinical. In this review the efficacy and usage of TP receptor antagonists for bronchial asthma was discussed.

Topics: Asthma; Benzoquinones; Bridged Bicyclo Compounds; Bronchi; Bronchial Hyperreactivity; Carbazoles; Fatty Acids, Monounsaturated; Heptanoic Acids; Humans; Prostaglandins; Receptors, Thromboxane; Sulfonamides; Thromboxane A2

It has been considered that thromboxane A2 (TXA2) is involved in the development of bronchial hyperresponsiveness (BHR), a characteristic feature of asthma. To ensure the involvement of TXA2 in BHR of asthma, effects of a 1-week treatment with two orally active TXA2 antagonists, BAY u 3405 and S-1452, on BHR were examined in 10 and 13 patients with stable asthma, respectively, in two consecutive double-blinded, randomized, placebo-controlled, two-phase crossover studies. Provocative concentration of methacholine causing a 20% fall in FEV1 (PC20-FEV1) with BAY u 3405 (0.78 (GSEM, 1.50) mg/ml) was significantly greater than the value with placebo (0.65 (GSEM, 1.46) mg/ml) (ratio 1.23 times, 95% CI 1.01 to 1.46: P = 0.0401). PC20-FEV1 was also significantly increased with S-1452 (0.43 (GSEM, 1.39) mg/ml) compared with placebo (0.29 (GSEM, 1.27) mg/ml) (ratio 1.75 times, 95% CI 1.05 to 2.45: P = 0.0189). Baseline pulmonary function was not altered by these treatments. These results may ensure that TXA2 is significantly involved in the BHR of asthma while the degree of contribution may be small.

Topics: Adolescent; Adult; Airway Resistance; Asthma; Bridged Bicyclo Compounds; Bronchial Hyperreactivity; Bronchoconstrictor Agents; Carbazoles; Cross-Over Studies; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Middle Aged; Prostaglandin Antagonists; Sulfonamides; Thromboxane A2