Potential synergistic effects of novel hematopoietic prostaglandin D synthase inhibitor TAS-205 and different types of anti-allergic medicine on nasal obstruction in a Guinea pig model of experimental allergic rhinitis

Hiroki Aoyagi, Daisuke Kajiwara, Kenta Tsunekuni, Katsunao Tanaka, Kazuhisa Miyoshi, Noriyasu Hirasawa

Research output: Contribution to journalArticlepeer-review

Abstract

Nasal obstruction is one of the most bothersome symptoms of allergic rhinitis (AR) affecting sleep-related quality of life in AR patients. Although several treatments were tested to control nasal obstruction, some patients with moderate to severe AR do not respond to current treatments, including the combined administration of different types of anti-allergic medicine. Thus, new options for AR treatment are needed. This study aimed to evaluate the effects of combined treatment with a novel inhibitor of hematopoietic prostaglandin D synthase (HPGDS), TAS-205, and different types of anti-allergic medicine on nasal obstruction in AR. Firstly, we demonstrated that TAS-205 selectively inhibited prostaglandin D2 (PGD2) synthesis in an enzymatic assay in a cell-based assay and in vivo models of AR. Moreover, treatment with TAS-205 alone suppressed eosinophil infiltration into the nasal cavity and late phase nasal obstruction. The combined administration of TAS-205 with montelukast, a cysteinyl leukotriene receptor 1 antagonist, showed significant additive inhibitory effects on eosinophil infiltration and late phase nasal obstruction compared to treatment with each agent alone. In contrast, concomitant treatment with TAS-205 and fexofenadine, a histamine H1 blocker, showed inhibitory effects on late phase and early phase nasal obstruction, although the magnitude of the inhibitory effects upon combined administration was comparable to that of each single treatment. These results suggest that combined treatment with an HPGDS inhibitor and different types of anti-allergic medicine may be a promising strategy to control nasal obstruction in AR patients.

Original languageEnglish
Article number173030
JournalEuropean Journal of Pharmacology
Volume875
DOIs
Publication statusPublished - 2020 May 15

Keywords

  • Allergic rhinitis
  • Hematopoietic prostaglandin D synthase
  • Histamine H antagonist
  • Leukotriene receptor antagonist
  • Prostaglandin D
  • TAS-205

ASJC Scopus subject areas

  • Pharmacology

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