OxyFile #116

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

Author:  Asano M; Imai T; Inoue H; Masunaga T; Inamura N; 
         Yatabe T; Hiroi J; Nakahara K; Notsu Y; Takishima T 

Address: Exploratory Research Laboratories, Fujisawa 
         Pharmaceutical Co., Ltd., Tsukuba Research Laboratories,
         Ibaraki, Japan. 

Source:  Agents Actions, 1993 Mar, 38:3-4, 171-7 

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, FR110302, 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 of Rrs to acetylcholine. Guinea pigs were 
exposed to 2.5 ppm ozone for 1 h. In a control group of guinea 
pigs, delta log 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 delta log 
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, 
delta log Dmin (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 delta log 
Dmin (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.