An agent that releases basophil and mast cell histamine but blocks cyclooxygenase and lipoxygenase metabolism of arachidonic acid inhibits immunoglobulin E-mediated asthma in rhesus monkeys.
An inhibitor of the lipoxygenase and cyclooxygenase pathways of arachidonic acid metabolism, BW755C, was evaluated with the rhesus monkey model of IgE-mediated asthma. BW755C was found to release histamine from human and rhesus peripheral blood leukocytes and rhesus bronchial lavage cells. BW755C did not induce a rhesus airway response but inhibited antigen-induced airway changes in pulmonary resistance and dynamic compliance. The results demonstrated that a lipoxygenase and cyclooxygenase inhibitor that is a histamine releaser may inhibit some pulmonary function abnormalities of an IgE-mediated response and suggested that histamine has a minor role as a stimulator of airway reaction in this model. This was supported by studies showing failure of the histamine H1 blocker pyrilamine maleate to inhibit the antigen-induced airway response. Although BW755C has been shown to be a lipoxygenase and cyclooxygenase inhibitor, it is not established that the inhibiting action of this agent on an antigen-induced airway response is due to an effect on arachidonate metabolism in the lung.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D001491:Basophils / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors; D008251:Macaca / Q000276:immunology*; D008253:Macaca mulatta / Q000276:immunology*; D008407:Mast Cells / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology*
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D007073:Immunoglobulin E; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine