The effect of an orally active leukotriene D4/E4 antagonist, LY171883, on antigen-induced airway responses in allergic sheep

Prostaglandins
William M AbrahamG A Chapman

Abstract

Leukotriene (LT) D4 is a putative mediator of allergic asthma: inhaled LTD4 produces early and late increases in specific lung resistance (SRL) and slows tracheal mucus velocity (TMV) similar to inhaled antigen. In this study we examined the effects of an orally active LTD4/LTE4 antagonist, LY171883 [1-less than 2-Hydroxy-3-propyl-4-less than 4-(1H-Tetrazol-5-yl) Butoxy greater than Phenyl greater than Ethanone], on early and late changes in SRL and TMV following airway challenge with Ascaris suum antigen in conscious allergic sheep. SRL and TMV were measured before and up to 8 h and 24 h after antigen challenge after either LY171883 (30 mg/kg, p.o. 2 h before challenge) or placebo pretreatment. After placebo pretreatment antigen challenge resulted in significant early (483% over baseline) and late (221% over baseline) increases in SRL (n = 9). LY171883 pretreatment, however, significantly reduced the early increase in SRL (163% over baseline) and blocked the late response. LY171883 did not prevent the antigen-induced fall in TMV from 5-8 h post challenge (n = 6), but TMV recovered more rapidly in the drug trial returning to baseline values by 24 h. These results suggest that the generation of LTD4, and its metabolite LTE4, dur...Continue Reading

References

Nov 1, 1977·Clinical Allergy·D W CockcroftF E Hargreave
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Apr 1, 1980·Prostaglandins·J F Burka, N A Paterson
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Citations

Feb 26, 1991·European Journal of Pharmacology·K M MettersA W Ford-Hutchinson
Jan 1, 1991·Annals of the New York Academy of Sciences·N J CuthbertP J Gardiner
Dec 1, 1988·The American Review of Respiratory Disease·W M AbrahamL D Yerger
Oct 31, 2002·American Journal of Respiratory and Critical Care Medicine·Juan R SabaterWilliam M Abraham
Jun 5, 2004·European Journal of Pharmacology·Aileen HouseRichard W Chapman
Mar 1, 1993·Prostaglandins, Leukotrienes, and Essential Fatty Acids·W M AbrahamJ Hallmon
Apr 1, 1989·Journal of Veterinary Internal Medicine·B Hansen
Jan 1, 1988·Annals of the New York Academy of Sciences·W M Abraham
Jan 1, 1988·Pediatric Pulmonology·W M Abraham, A Wanner

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