Effects of TAK-427 on acute nasal symptoms and nasal obstruction in guinea pig model of experimental allergic rhinitis

Eur J Pharmacol. 2003 Aug 29;476(3):239-47. doi: 10.1016/s0014-2999(03)02188-5.

Abstract

TAK-427 (2-[6-[[3-[4-(diphenylmethoxy)piperidino]propyl]amino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionic acid dihydrate) is a novel anti-allergic agent that has both histamine H1-receptor antagonist and anti-inflammatory activities. In this study, we evaluated the efficacy of TAK-427 on acute nasal responses and nasal obstruction using various guinea pig models of allergic rhinitis. TAK-427 inhibited the histamine-induced nasal reactions with an ID50 value of 0.633 mg/kg, p.o. TAK-427 (0.1-10 mg/kg, p.o.) and most histamine H1-receptor antagonists tested inhibited the increase in intranasal pressure, nasal hypersecretion, sneezing and nasal itching caused by a single antigen challenge in sensitized guinea pigs. In addition, TAK-427 (0.3, 30 mg/kg, p.o.) significantly inhibited the development of nasal obstruction when sensitized guinea pigs were repeatedly challenged via inhalation with Japanese cedar pollen, whereas the histamine H1-receptor antagonist, azelastine (1 mg/kg, p.o.), and ketotifen (1 mg/kg, p.o.) were without effect. These results suggest that TAK-427 might not only suppress acute nasal symptoms but also ameliorate nasal obstruction via the effects other than those as a histamine H1-receptor antagonist.

Publication types

  • Comparative Study

MeSH terms

  • Acute Disease
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Disease Models, Animal
  • Guinea Pigs
  • Histamine / metabolism
  • Histamine H1 Antagonists / pharmacology*
  • Imidazoles / pharmacology*
  • Male
  • Nasal Obstruction / drug therapy*
  • Nasal Obstruction / immunology
  • Ovalbumin / immunology
  • Pollen / immunology
  • Pyridazines / pharmacology*
  • Rhinitis, Allergic, Perennial / drug therapy*
  • Rhinitis, Allergic, Perennial / immunology
  • Rhinitis, Allergic, Perennial / physiopathology
  • Rhinitis, Allergic, Seasonal / drug therapy*
  • Rhinitis, Allergic, Seasonal / immunology
  • Rhinitis, Allergic, Seasonal / physiopathology
  • Sneezing / drug effects
  • Sneezing / immunology

Substances

  • 2-(6-((3-(4-(diphenylmethoxy)piperidino)propyl)amino)imidazo(1,2-b)pyridazin-2-yl)-2-methylpropionic acid
  • Anti-Inflammatory Agents
  • Histamine H1 Antagonists
  • Imidazoles
  • Pyridazines
  • Histamine
  • Ovalbumin