Inhibitory effect of a novel quinolinone derivative, TA-270, on asthmatic inflammatory responses in sensitized guinea pigs.
TA-270 (4-hydroxy-1-methyl-3-octyloxy-7-sinapinoylamino-2(1H)- quinolinone), a novel quinolinone derivative, was designed as an antioxidant to scavenge reactive oxygen species. Here, we investigated the effects of TA-270, in comparison with several antiasthmatic drugs, on asthmatic responses as induced by ovalbumin in sensitized guinea pigs. When orally administered 1 h before and 3 h after the antigen challenge, TA-270 at 10 mg/kg and higher doses significantly inhibited both immediate and late responses in airway resistance induced by the antigen. The inhibitory effects were comparable to or superior, at least under the present experimental conditions, to those of several clinically used antiasthmatic drugs. Furthermore, TA-270, in a dose-dependent manner, reduced accumulation of pulmonary inflammatory cells, especially eosinophils, and significantly reversed the airway hyperresponsiveness to acetylcholine 24 h after the antigen challenge. These results suggest that TA-270 may be of therapeutic use for bronchial asthma.
Aoki
Y
Y
Central Research Laboratories, Dainippon Ink and Chemicals, Inc., 631 Sakado, Chiba 285-8668, Sakura, Japan.
Ishiwara
M
M
Koda
A
A
Takagaki
H
H
D000109:Acetylcholine / Q000494:pharmacology; D000403:Airway Resistance / Q000187:drug effects* / Q000276:immunology; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects* / Q000276:immunology; D002934:Cinnamates / Q000494:pharmacology* / Q000627:therapeutic use; D006168:Guinea Pigs; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D008297:Male; D015363:Quinolones / Q000494:pharmacology* / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000494:pharmacology
D018927:Anti-Asthmatic Agents; D000975:Antioxidants; D002934:Cinnamates; D015363:Quinolones; C420451:TA 270; D014665:Vasodilator Agents; D000109:Acetylcholine