Effects of ONO-6950, a novel dual cysteinyl leukotriene 1 and 2 receptors antagonist, in a guinea pig model of asthma

European Journal of Pharmacology
Yasuo YonetomiKazuhito Kawabata

Abstract

We assessed in this study the anti-asthmatic effects of ONO-6950, a novel cysteinyl leukotriene 1 (CysLT1) and 2 (CysLT2) receptors dual antagonist, in normal and S-hexyl glutathione (S-hexyl GSH)-treated guinea pigs, and compared these effects to those of montelukast, a CysLT1 selective receptor antagonist. Treatment with S-hexyl GSH reduced animals LTC4 metabolism, allowing practical evaluation of CysLT2 receptor-mediated airway response. ONO-6950 antagonized intracellular calcium signaling via human and guinea pig CysLT1 and CysLT2 receptors with IC50 values of 1.7 and 25 nM, respectively (human receptors) and 6.3 and 8.2 nM, respectively (guinea pig receptors). In normal guinea pigs, both ONO-6950 (1 or 0.3 mg/kg, p.o.) and the CysLT1 receptor antagonist montelukast (0.3 or 0.1 mg/kg, p.o.) fully attenuated CysLT1-mediated bronchoconstriction and airway vascular hyperpermeability induced by LTD4. On the other hand, in S-hexyl GSH-treated guinea pigs ONO-6950 at 3 mg/kg, p.o. or more almost completely inhibited bronchoconstriction and airway vascular hyperpermeability elicited by LTC4, while montelukast showed only partial or negligible inhibition of these airway responses. In ovalbumin sensitized guinea pigs, treatment with...Continue Reading

References

Jun 14, 2000·The Journal of Biological Chemistry·C E HeiseJ F Evans
Nov 7, 2001·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·H MitaK Akiyama
Sep 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Elizabeth A MellorJoshua A Boyce
Oct 2, 2003·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·D J FigueroaJ F Evans
Oct 31, 2003·The Journal of Allergy and Clinical Immunology·Richard J Martin
Jul 2, 2005·The Journal of Allergy and Clinical Immunology·Gail M GauvreauDonald W MacGlashan
Nov 19, 2005·American Journal of Respiratory and Critical Care Medicine·John J LimaKathleen Barnes
Nov 6, 2007·The New England Journal of Medicine·Marc Peters-Golden, William R Henderson
Feb 18, 2010·The Journal of Allergy and Clinical Immunology·J Mark FitzGerald, Neal Shahidi
Nov 10, 2010·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·P Montuschi, M L Peters-Golden
Jul 19, 2013·The Journal of Asthma : Official Journal of the Association for the Care of Asthma·Rakesh Kumar SinghAbhijit Ray
Dec 20, 2013·Expert Opinion on Pharmacotherapy·Hiroto Matsuse, Shigeru Kohno
Oct 5, 2015·Allergology International : Official Journal of the Japanese Society of Allergology·Tomohiko SekiokaTakeshi Nabe

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Citations

Dec 8, 2019·Nature Communications·Anastasiia GusachVadim Cherezov
May 15, 2018·The Journal of Clinical Investigation·Takehiko YokomizoTakao Shimizu

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