Inhibitory Effect of a TP-Receptor Antagonist, S-1452, on Antigen-Induced Nasal Plasma Exudation in Guinea Pig Model for Allergic Rhinitis

Abstract

S-1452, a selective thromboxane (Tx) A₂ receptor (TP-receptor) antagonist, was evaluated in antigen- and U-46619 (a TxA₂ mimetic)-induced guinea pig nasal plasma exudation models. Exposure of the nasal cavity of actively sensitized guinea pigs to aerosolized ovalbumin (OA) caused marked exudation of dye into both the nasal mucosa and nasal airway lumen. These responses were significantly inhibited by S-1452 (30 mg/kg, p.o.) as well as an H₁-antihistamine, diphenhydramine (5 mg/kg, i.v.). In addition, exposure of the nasal cavity of nonsensitized guinea pigs to aerosolized U-46619 or histamine also resulted in nasal plasma exudation, and S-1452 (1 mg/kg, p.o.) almost completely suppressed the U-46619-induced response but did not affect the histamine-induced one, even at a high dose of 30 mg/kg. These results indicate that TxA₂ as well as histamine may play an important role in antigen-induced nasal plasma exudation in guinea pigs, and S-1452 can be expected to be useful for the treatment of allergic rhinitis.

Participation in cysteinyl leukotrienes and thromboxaneA2 in nasal congestion model in Brown Norway rats

“…Seratrodast and ramatroban, TXA 2 receptor antagonists, also significantly inhibited both early and late phase nasal congestion. It is well known that cysLTs increase nasal mucosal blood flow by dilating blood vessels [16], and TXA 2 induce swelling of nasal mucosa by plasma extravasation, which are major causes of nasal congestion [17]. Recent studies show that cys-LTs and TXA 2 are likely released from various inflammation cells, such as mast cells and eosinophils, by antigenantibody reaction [18], and these mediators then induce an increase in nasal vascular permeability that produces tissue edema in humans and guinea pigs [19][20][21][22].…”

A Pilot Study Investigating the Impact of Topical Nasal Steroid Spray in Allergic Rhinitis Patients with Dry Eye

“…Allergic rhinitis (AR) is a type 1 hypersensitivity reaction caused by the development of immunoglobulin E in the rhino-ocular mucosa due to allergens, and it is diagnosed based on the history, a physical examination, and appropriate skin testing [8]. A significant relationship between dry eye and AR in adults has been reported [9].…”

Effects of Fexofenadine Hydrochloride in a Guinea Pig Model of Antigen-Induced Rhinitis

“…It has also been reported that histamine, leukotrienes, and thromboxane, are involved in the mechanism of development of allergic rhinitis in guinea pigs [6,9,10,[12][13][14][15][16][17][18] .…”

“…TXB 2 is found in the nasal lavage fl uid from patients with allergic rhinitis [42,43] as well as the sensitized guinea pigs [10,14,15] after antigen provocation. In addition, it has been reported that U-46619, a TXA 2 mimetic, increased nasal vascular permeability [14,18] and nasal airway resistance [14,15] in guinea pigs, and that a TXA 2 antagonist attenuated the increase in nasal airway resistance in sensitized guinea pigs [6,10,14,15,17] . In allergic rhinitis patients, it was reported that a selective TXA 2 antagonist, ramatroban approved for the treatment of allergic rhinitis in Japan in 2000, attenuated the increase in nasal airway resistance [44,45] .…”

“…That is, the experimental animals also exhibit sneezing [6][7][8][9][10] , nasal secretion [9] and nasal obstruction [6][7][8][9][10][11][12][13][14][15][16][17] . It has been demonstrated that histamine [10,12,14,16] , leukotrienes [9,10,12,13,16] , and thromboxane [6,10,12,14,15,17,18] are involved in the mechanism of development of the pathology in these models. Accordingly, these guinea pig models have come to be widely used for evaluation of the pharmacological effects of drugs being developed for the treatment of allergic rhinitis.…”