Effects of RS-601, a novel leukotriene D(4)/thromboxane A(2) dual receptor antagonist, on asthmatic responses in guinea pigs.
The effects of 4-[4-[5,5,6,6,6-pentafluoro-1-(4-fluorobenzene-sulfonamido)hexyl]phenyl]butyric acid (RS-601), a novel leukotriene D(4) (LTD(4))/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 (LTD(4) receptor antagonist) and S-1452 (TxA(2) receptor antagonist). RS-601 inhibited the increase in airway resistance caused by LTD(4) and TxA(2) mimetic compound, U-46619, but not by histamine. RS-601 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 RS-601 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.
Yamada
Takatoshi
T
Department of Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
Takahashi
Yoshimasa
Y
Ishizaki
Masayuki
M
Musoh
Keiichi
K
Ohashi
Tetsuo
T
Tanaka
Hiroyuki
H
Inagaki
Naoki
N
Nagai
Hiroichi
H
D000403:Airway Resistance / Q000187:drug effects* / Q000276:immunology*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001249:Asthma / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced; D001985:Bronchial Provocation Tests; D002087:Butyrates / Q000494:pharmacology*; D004195:Disease Models, Animal; D005466:Fluorocarbons; D006168:Guinea Pigs; D020024:Leukotriene Antagonists; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D018077:Receptors, Leukotriene; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors*; D012119:Respiration / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology*
C479879:4-(4-(5,5,6,6,6-pentafluoro-1-(4-fluorobenzene-sulfonamido)hexyl)phenyl)butyric acid; D018927:Anti-Asthmatic Agents; D002087:Butyrates; D005466:Fluorocarbons; D020024:Leukotriene Antagonists; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D018077:Receptors, Leukotriene; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013449:Sulfonamides; C083169:leukotriene D4 receptor