The effect of a novel leukotriene C4/D4 antagonist, BAY-x-7195, on experimental allergic reactions

Prostaglandins. 1995 Nov-Dec;50(5-6):269-85. doi: 10.1016/0090-6980(95)00135-2.

Abstract

The effects of a novel leukotriene (LT) C4/D4 antagonist, BAY-x-7195 on experimental allergic reactions in airway and skin were compared to that of ONO-1078. BAY-x-7195 showed an antagonistic action to LTD4-induced bronchoconstriction in vitro and in vivo. In in vitro experiments, BAY-x-7195 inhibited LTD4-induced contraction of isolated guinea pig tracheal muscle (pA2 = 8.03). BAY-x-7195 at doses of 3-30 mg/kg clearly inhibited LTD4-induced increases in respiratory resistance (Rrs) in guinea pigs. In contrast, BAY-x-7195 inhibited significantly U-46619-induced increases in Rrs at a dose of 30 mg/kg in guinea pigs. BAY-x-7195 at doses of 3-30 mg/kg inhibited the aerosolized antigen-induced biphasic increase in Rrs in guinea pigs. Moreover BAY-x-7195 inhibited repeated aeroantigen-induced airway hyperreactivity in guinea pigs. In mice, aeroantigen-induced airway inflammation were clearly inhibited by BAY-x-7195. These results show the efficacy of BAY-x-7195 against the antigen-induced increase in airway resistance and antigen-induced airway hyperreactivity in guinea pigs and mice, probably due to anti-LTD4 antagonistic action and the inhibition of antigen-induced airway inflammation.

MeSH terms

  • Airway Resistance / drug effects
  • Animals
  • Bronchoalveolar Lavage
  • Bronchoconstriction / drug effects
  • Chromones / pharmacology
  • Guinea Pigs
  • Hydroxy Acids / pharmacology*
  • Hypersensitivity / metabolism*
  • Immunoglobulin E / pharmacology
  • Inflammation / metabolism
  • Interleukin-5 / metabolism
  • Leukocytes / drug effects
  • Leukocytes / metabolism
  • Leukotriene C4 / antagonists & inhibitors*
  • Leukotriene C4 / pharmacology
  • Leukotriene D4 / antagonists & inhibitors*
  • Leukotriene D4 / pharmacology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Muscle Contraction / drug effects
  • Ovalbumin / immunology
  • Ovalbumin / pharmacology
  • Prednisolone / pharmacology
  • Skin / metabolism
  • Trachea / drug effects

Substances

  • Chromones
  • Hydroxy Acids
  • Interleukin-5
  • Leukotriene C4
  • Immunoglobulin E
  • Leukotriene D4
  • Ovalbumin
  • Prednisolone
  • pranlukast
  • BAY x 7195