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

• Published in: European journal of pharmacology 2003-08, Vol.476 (3), p.239-247
• Main Authors: Fukuda, Shigeru, Midoro, Katsuo, Gyoten, Michiyo, Kawano, Yasuhiko, Ashida, Yasuko, Nabe, Takeshi, Kohno, Shigekatsu, Nagaya, Hideaki
• Format: Article
• Language: English
• Subjects: Acute Disease; Allergic rhinitis; Animals; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Cedar pollen; Disease Models, Animal; Guinea Pigs; Histamine - metabolism; Histamine and antagonists. Allergy; Histamine H 1-receptor antagonist; Histamine H1 Antagonists - pharmacology; Imidazoles - pharmacology; Male; Medical sciences; Nasal acute symptom; Nasal obstruction; Nasal Obstruction - drug therapy; Nasal Obstruction - immunology; Ovalbumin - immunology; Pharmacology. Drug treatments; 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; TAK-427 {2-[6-[[3-[4-(diphenylmethoxy) piperidino]propyl]amino]imidazo[1,2- b]pyridazin-2-yl]-2-methylpropionic acid dihydrate}
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(03)02188-5

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 H 1-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 ID 50 value of 0.633 mg/kg, p.o. TAK-427 (0.1–10 mg/kg, p.o.) and most histamine H 1-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 H 1-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 H 1-receptor antagonist.