title: A 5-lipoxygenase inhibitor, FR110302, inhibits ozone-induced airway hyperresponsiveness in guinea pigs and dogs.
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.
authors.affiliation: Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Tsukuba Research Laboratories, Ibaraki, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Asano
authors.forename: T
authors.initials: T
authors.lastname: Imai
authors.forename: H
authors.initials: H
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Masunaga
authors.forename: N
authors.initials: N
authors.lastname: Inamura
authors.forename: T
authors.initials: T
authors.lastname: Yatabe
authors.forename: J
authors.initials: J
authors.lastname: Hiroi
authors.forename: K
authors.initials: K
authors.lastname: Nakahara
authors.forename: Y
authors.initials: Y
authors.lastname: Notsu
authors.forename: T
authors.initials: T
authors.lastname: Takishima
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000284:Administration, Oral; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000188:drug therapy*; D004285:Dogs; D006168:Guinea Pigs; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009284:Naphthols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010126:Ozone / Q000633:toxicity; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016859:Lipoxygenase Inhibitors; D009284:Naphthols; D011804:Quinolines; C074243:FR 110302; D010126:Ozone; D000109:Acetylcholine