The orally active antiallergic compound, LC-6 (trans-2,3b,4,5,7,8b,9,10-octahydronaphtho[1,2-c:5,6-C] dipyrazole) inhibits the arachidonate lipoxygenase enzyme.
Trans-2,3,4,5,7,8b,9,10-octahydronaphtho[1,2-C:5,6-C]dipyrazole (LC-6), which is active in vivo when administered orally, inhibits histamine release from peritoneal rat mast cells and human basophils in vitro. LC-6.2Cl blocks both IgE-mediated and non-IgE-mediated histamine release. Histamine release induced by antigen, dextran, compound 48/80, or the Ca2+ ionophore A23187 was effectively inhibited. The in vitro data indicate that LC6.2HCl has the capacity to inhibit the mediator release phase of anaphylaxis. The drug has the ability to inhibit arachidonate lipoxygenase activity. The IC50 for IgE-mediated histamine release inhibition is in good agreement with the IC50 for inhibition of arachidonate lipoxygenase activity. The data indicate that LC-6 acts in vivo by blocking the release of mediators; its activity may be explained by its ability to stop the synthesis of lipoxygenase-derived arachidonic acid products.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001491:Basophils / Q000187:drug effects*; D006634:Histamine H1 Antagonists; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D016859:Lipoxygenase Inhibitors; D008407:Mast Cells / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats
D001095:Arachidonic Acids; D006634:Histamine H1 Antagonists; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D016718:Arachidonic Acid; C016885:LC 6