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.