Effect of TA-270, a novel quinolinone derivative, on antigen-induced nasal blockage in a guinea pig model of allergic rhinitis.
TA-270 (4-hydroxy-1-methyl-3-octyloxy-7-sinapinoylamino-2(1H)-quinolinone) is a novel quinolinone derivative that has been demonstrated to possess an anti-oxidative activity against peroxynitrite, a potent oxidant, that is generated by the reaction of nitric oxide with superoxide anions. The current study describes the inhibitory effect of TA-270 on the biphasic nasal blockage induced by repeated antigen challenge in an allergic rhinitis guinea pig model. In the present in vitro study, TA-270 potently inhibited the oxidative reaction induced by peroxynitrite (IC(50)=79 nM). In addition, TA-270 (0.3-30 mg/kg, p.o.) dose-dependently inhibited peroxynitrite (3 mM, 10 mul/nostril)-induced nasal blockage in guinea pigs. In the antigen-induced allergic rhinitis model, TA-270 (0.3, 3, and 30 mg/kg, p.o.) given 1 h before the antigen challenge suppressed early phase nasal blockage by 36%, 42%, and 63%, respectively. Furthermore, TA-270 (0.3, 3, and 30 mg/kg, p.o.) showed a relatively strong suppression of late phase nasal blockage (39%, 62%, and 72%, respectively). The late phase nasal blockage was significantly inhibited (61%) even when TA-270 (30 mg/kg, p.o.) was administered 18 h before the antigen challenge. In conclusion, TA-270 improved antigen-induced nasal blockage, probably through its peroxynitrite scavenging action, and the effect was sustained for at least 18 h. Thus, TA-270 would be expected to relieve nasal blockage in allergic rhinitis patients.
Mizutani
Nobuaki
N
Department of Pharmacology, Kobe Pharmaceutical University, 4-19-1 Motoyamakita, Higashinada, Kobe 658-8558, Japan. mizutani@kobepharma-u.ac.jp
Aoki
Yasuo
Y
Nabe
Takeshi
T
Ishiwara
Mitsuteru
M
Yoshino
Shin
S
Takagaki
Hidetsugu
H
Kohno
Shigekatsu
S
D000485:Allergens / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000276:immunology*; D028203:Cedrus; D002934:Cinnamates / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D017998:Leukotriene D4 / Q000378:metabolism; D008297:Male; D015508:Nasal Obstruction / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism; D011058:Pollen / Q000276:immunology; D015363:Quinolones / Q000494:pharmacology* / Q000627:therapeutic use*; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D000485:Allergens; D000941:Antigens; D002934:Cinnamates; D015363:Quinolones; C420451:TA 270; D030421:Peroxynitrous Acid; D017998:Leukotriene D4