5-Lipoxygenase inhibitors and allergic conjunctivitis reactions in the guinea-pig.

Abstract

The role of leukotrienes as mediators of microvascular permeability changes (assessed through the accumulation of [99mTc]albumin) associated with immediate hypersensitivity reactions in the guinea-pig conjunctiva was investigated by means of two novel, structurally dissimilar 5-lipoxygenase inhibitors, L-651,392 and L-651,896. Both compounds, when applied topically in vivo to the eyes of sensitized guinea-pigs as a 0.1% suspension significantly inhibited 5-lipoxygenase in the conjunctiva as assessed by ex vivo challenge with either antigen or ionophore A23187 and measurement of the release of leukotriene B4-immunoreactive material. Topical application of antigen (either single challenge or 2 challenges separated by 24 h) to the eyes of sensitized guinea-pigs produced changes in conjunctival permeability which were blocked in part by either mepyramine (H1-receptor antagonist) or the 5-lipoxygenase inhibitors. Combinations of mepyramine and L-651,896 resulted in near complete suppression of the permeability response, suggesting that the reaction is mediated only by histamine and leukotrienes.

• Authors: D Garceau, A W Ford-Hutchinson, S Charleson
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 143 Issue 1 Pg. 1-7 (Nov 03 1987) ISSN: 0014-2999 [Print] Netherlands
• PMID: 2826183 (Publication Type: Journal Article)

Chemical References

• Benzofurans
• Lipoxygenase Inhibitors
• Phenothiazines
• SRS-A
• Leukotriene B4
• Calcimycin
• 4-bromo-2,7-dimethoxy-3H-phenothiazin-3-one
• L 651896
• Arachidonate Lipoxygenases
• Pyrilamine

Topics

• Animals
• Arachidonate Lipoxygenases (antagonists & inhibitors)
• Benzofurans (pharmacology)
• Calcimycin (pharmacology)
• Capillary Permeability (drug effects)
• Conjunctivitis, Allergic (immunology, physiopathology)
• Guinea Pigs
• Leukotriene B4 (physiology)
• Lipoxygenase Inhibitors
• Male
• Phenothiazines (pharmacology)
• Pyrilamine (pharmacology)
• SRS-A (physiology)