Effects of TAK-427 on acute nasal symptoms and nasal obstruction in guinea pig model of experimental allergic rhinitis.
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.
Fukuda
Shigeru
S
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd, 2-17-85, Juso-Honmachi, Yodogawa, Osaka 532-8686, Japan. Fukuda_Shigeru@takeda.co.jp
Midoro
Katsuo
K
Gyoten
Michiyo
M
Kawano
Yasuhiko
Y
Ashida
Yasuko
Y
Nabe
Takeshi
T
Kohno
Shigekatsu
S
Nagaya
Hideaki
H
D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006632:Histamine / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D015508:Nasal Obstruction / Q000188:drug therapy* / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011058:Pollen / Q000276:immunology; D011724:Pyridazines / Q000494:pharmacology*; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D012912:Sneezing / Q000187:drug effects / Q000276:immunology
C469683:2-(6-((3-(4-(diphenylmethoxy)piperidino)propyl)amino)imidazo(1,2-b)pyridazin-2-yl)-2-methylpropionic acid; D000893:Anti-Inflammatory Agents; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D011724:Pyridazines; D006632:Histamine; D010047:Ovalbumin