Agents and Actions

, Volume 38, Issue 1–2, pp 171–177 | Cite as

A 5-lipoxygenase inhibitor, FR110302, inhibits ozone-induced airway hyperresponsiveness in guinea pigs and dogs

  • Masayuki Asano
  • Takumi Imai
  • Hiroshi Inoue
  • Taro Masunaga
  • Noriaki Inamura
  • Takumi Yatabe
  • Jun Hiroi
  • Kunio Nakahara
  • Yoshitada Notsu
  • Tamotsu Takishima
Allergy and Histamine
Received:
Accepted:

Abstract

Airway hyperresponsiveness is a key feature of asthma, and attenuating airway hyperresponsiveness is an important part of asthma therapy. In the present study we examined the inhibitory effect of a potent 5-lipoxygenase inhibitor, FR 110302, on airway hyperresponsiveness induced by ozone exposure in guinea pigs and dogs. Respiratory resistance (Rrs) was measured by a forced oscillation method. Airway responsiveness was determined from the dose-response curve ofRrs to acetylcholine. Guinea pigs were exposed to 2.5 ppm ozone for 1 h. In a control group of guinea pigs, Δlog PC100 (the index of the ozone-induced airway hyperresponsiveness) was 0.58±0.04 (log mg/ml). Treatment with FR110302 (10 or 100 mg/kg p.o.) significantly diminished Δlog PC100 (10 mg/kg; 0.22±0.10; 100 mg/kg; 0.11±0.06). Dogs were exposed to 3 ppm ozone for 2 h. In a control group of dogs, ΔlogDmin (another index of the ozone-induced airway hyperresponsiveness) was 1.24±0.15 (log unit). Treatment with FR110302 (1 or 3.2 mg/kg p.o.) significantly diminished ΔlogDmin (1 mg/kg: 0.60±0.18; 3.2 mg/kg: 0.27±0.12). These results suggest that FR110302 may be a useful drug for attenuating airway hyperresponsiveness in asthmatic patients.

Keywords

Asthma Ozone Acetylcholine Asthmatic Patient Airway Hyperresponsiveness 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Birkhäuser Verlag 1993

Authors and Affiliations

  • Masayuki Asano
    • 1
  • Takumi Imai
    • 2
  • Hiroshi Inoue
    • 3
  • Taro Masunaga
    • 2
  • Noriaki Inamura
    • 1
  • Takumi Yatabe
  • Jun Hiroi
    • 2
  • Kunio Nakahara
    • 1
  • Yoshitada Notsu
    • 1
  • Tamotsu Takishima
    • 3
  1. 1.Exploratory Research LaboratoriesFujisawa Pharmaceutical Co., Ltd., Tsukuba Research LaboratoriesTsukuba, IbarakiJapan
  2. 2.Product Development LaboratoriesFujisawa Pharmaceutical Co., Ltd.OsakaJapan
  3. 3.First Department of Internal MedicineTohoku University School of MedicineSendaiJapan

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