Effects of RS-601, a novel leukotriene D4/thromboxane A2 dual receptor antagonist, on asthmatic responses in guinea pigs

The effects of 4-[4-[5,5,6,6,6-pentafluoro-1-(4-fluorobenzene-sulfonamido)hexyllphenyllbutyric acid (IRS-601), a novel leukotriene D-4 (LTD4)/thromboxane A(2) (TxA(2)) dual receptor antagonist, on bronchial asthmatic responses in guinea pigs were examined. The effects were compared with those of pranlukast (LTD4 receptor antagonist) and S-1452 (TxA(2) receptor antagonist). RS-601 inhibited the increase in airway resistance caused by LTD4 and TxA2 mimetic compound, U-46619, but not by histamine. RS601 and pranlukast but not S-1452 inhibited an antigen-induced late asthmatic response. In addition, RS-601 inhibited an antigen-induced airway hyperresponsiveness (AHR), whereas pranlukast and S-1452 had no effect on the AHR. The antigen-induced increase in inflammatory cells in airway was not affected by all examined agents. Furthermore, bacterial lipopolysaccharide-induced AHR in guinea pigs was clearly suppressed by RS601 but not by pranlukast and S-1452. The increase in airway inflammatory cells caused by lipopolysaccharide was not affected by all three drugs. These findings indicate that RS-601 has a potent antiasthmatic efficacy, especially on AHR, but does not affect accumulation of eosinophils in the airways. Copyright (C) 2003 S. Karger AG, Basel.