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Effect of TA-270, a novel quinolinone derivative, on antigen-induced nasal blockage in a guinea pig model of allergic rhinitis.
Eur J Pharmacol. 2009 Jan 05; 602(1):138-42.EJ

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology, Kobe Pharmaceutical University, 4-19-1 Motoyamakita, Higashinada, Kobe 658-8558, Japan. mizutani@kobepharma-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19022242

Citation

Mizutani, Nobuaki, et al. "Effect of TA-270, a Novel Quinolinone Derivative, On Antigen-induced Nasal Blockage in a Guinea Pig Model of Allergic Rhinitis." European Journal of Pharmacology, vol. 602, no. 1, 2009, pp. 138-42.
Mizutani N, Aoki Y, Nabe T, et al. Effect of TA-270, a novel quinolinone derivative, on antigen-induced nasal blockage in a guinea pig model of allergic rhinitis. Eur J Pharmacol. 2009;602(1):138-42.
Mizutani, N., Aoki, Y., Nabe, T., Ishiwara, M., Yoshino, S., Takagaki, H., & Kohno, S. (2009). Effect of TA-270, a novel quinolinone derivative, on antigen-induced nasal blockage in a guinea pig model of allergic rhinitis. European Journal of Pharmacology, 602(1), 138-42. https://doi.org/10.1016/j.ejphar.2008.11.006
Mizutani N, et al. Effect of TA-270, a Novel Quinolinone Derivative, On Antigen-induced Nasal Blockage in a Guinea Pig Model of Allergic Rhinitis. Eur J Pharmacol. 2009 Jan 5;602(1):138-42. PubMed PMID: 19022242.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of TA-270, a novel quinolinone derivative, on antigen-induced nasal blockage in a guinea pig model of allergic rhinitis. AU - Mizutani,Nobuaki, AU - Aoki,Yasuo, AU - Nabe,Takeshi, AU - Ishiwara,Mitsuteru, AU - Yoshino,Shin, AU - Takagaki,Hidetsugu, AU - Kohno,Shigekatsu, Y1 - 2008/11/09/ PY - 2008/10/22/received PY - 2008/11/03/accepted PY - 2008/11/22/entrez PY - 2008/11/22/pubmed PY - 2009/10/8/medline SP - 138 EP - 42 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 602 IS - 1 N2 - 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. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/19022242/Effect_of_TA_270_a_novel_quinolinone_derivative_on_antigen_induced_nasal_blockage_in_a_guinea_pig_model_of_allergic_rhinitis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(08)01139-4 DB - PRIME DP - Unbound Medicine ER -