Effect of ONO-6950, a novel dual cysteinyl leukotriene 1 and 2 receptor antagonist, in guinea pig models of allergic rhinitis.

Abstract

This study evaluated the anti-rhinitic effects of ONO-6950, a novel dual antagonist of cysteinyl leukotriene 1 (CysLT) and 2 (CysLT) receptors, in guinea pig models of allergic rhinitis. First, in a conventional allergic rhinitis model without S-hexyl glutathione (S-hexyl GSH), both ONO-6950 (3 mg/kg, orally (p.o.)) and montelukast (0.3, 1, or 3 mg/kg, p.o.), a selective CysLTantagonist, significantly suppressed the increases in nasal airway resistance and inflammatory cell infiltration induced by ovalbumin (OVA) challenge, with comparable efficacy. Subsequently, in a model with S-hexyl GSH treatment to inhibit LTCmetabolism and enhance CysLTreceptor-mediated responses, ONO-6950 (0.3, 1, or 3 mg/kg, p.o.) dose-dependently and almost completely inhibited both immediate and late increases in nasal airway resistance and inflammatory cell infiltration, whereas montelukast showed only partial or negligible inhibition. These results indicate that ONO-6950 is effective against both CysLT-and CysLT-mediated rhinitic responses, and may offer a novel therapeutic option for patients with allergic rhinitis, particularly in cases refractory to CysLT-selective antagonists.