EFFECTS OF CS-518, A THROMBOXANE SYNTHASE INHIBITOR, ON THE ASTHMATICRESPONSE

The anti-asthmatic effects of CS-518 (sodium thyl)-4,5-dihydrobenzo[b] thiophene-6-carboxylate), a specific thromboxane A2 (TXA2) synthase in hibitor, were investigated in the ovalbumin-sensitized guinea pig asth matic model. Although CS-518 slightly inhibited (about 25%) whole bron choconstriction, it significantly inhibited the antigen-induced bronch oconstriction mediated by slow-reacting substance of anaphylaxis (SRS- A), which was not reduced by chlorpheniramine, a histamine H-1 antagon ist. On the other hand, indomethacin, a cyclooxygenase inhibitor, pote ntiated the SRS-A-mediated constriction. CS-518 strongly, and indometh acin slightly, suppressed the leukotriene D4-induced bronchoconstricti on. CS-518 clearly inhibited the antigen-induced airway hyperresponsiv eness, but this compound had no effect on the airway hyperresponsivene ss induced by U-46619, a TXA2-mimetic agent, and propranolol. These re sults suggest that CS-518 suppresses the development of bronchoconstri ction and airway hyperresponsiveness in asthmatic models by inhibition of TXA2 synthesis with the concomitant increase in bronchodilating pr ostaglandins such as prostaglandin E2 and prostaglandin I2.