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Abstract #6518 Published in IGR 3-2
Prevention of allergic inflammation by a novel prostaglandin receptor antagonist, S-5751
Arimura A; Yasui K; Kishino J; Asanuma F; Hasegawa H; Kakudo S; Ohtani M; Arita HJournal of Pharmacology and Experimental Therapeutics 2001; 298: 411-419
Prostaglandin (PG) D2, the major cyclooxygenase metabolite generated from immunologically stimulated mast cells, is thought to contribute to the pathogenesis of allergic diseases due to its various inflammatory effects. However, since no DP receptor antagonist has been developed as an antiallergic drug, the role of PGD2 in the pathogenesis of allergic diseases remains uncertain. Here, the authors report the in vivo efficacy of their newly established DP receptor antagonist, S-5751 (((Z)-7-((1R,2R,3S,5S)-2-(5-hydroxy benzo(b) thiophen-3-ylcarbonylamino)-10-norpinan-3-yl)hept-5- enoic acid)), using various allergic inflammation guinea pig models. In allergic rhinitis models, oral administration of S-5751 dramatically inhibited not only early nasal responses, as assessed by sneezing, mucosal plasma exudation, and nasal blockage, but also late responses such as mucosal plasma exudation and eosinophil infiltration. Even when S-5751 was administered after recovery from the early responses, these late phase responses were almost completely suppressed. In addition, S-5751 alleviated allergen-induced plasma exudation in the conjunctiva in an allergic conjunctivitis model and antigen-induced eosinophil infiltration into the lung in an asthma model. These findings provide evidence for the crucial role of PGD2 as a mediator of allergic inflammation in guinea pigs and suggest that DP receptor antagonists may be useful in the treatment of allergic diseases triggered by mast cell activation.
Dr A. Arimura, Discovery Research Laboratories, Shionogi & Co., Osaka, Japan. arimura@shionogi.co.jp
Classification:
11.15 Other drugs in relation to glaucoma (Part of: 11 Medical treatment)
