The antiallergic agent amoxanox suppresses SRS-A generation by inhibiting lipoxygenase.
Amoxanox has potent antiallergic activity because it inhibits the release of chemical mediators such as histamine and leukotrienes. We studied the in vitro effect of amoxanox on arachidonic acid metabolism, including the lipoxygenase and cyclooxygenase pathways. Amoxanox inhibited calcium ionophore A23187-induced formation of 5-HETE, LTB4, SRS-A (LTC4, LTD4 and LTE4), and 12-HETE in rat peritoneal resident monocytes. These results indicate that amoxanox inhibits 5- and 12-lipoxygenases. The compound, however, did not affect the formation of TXB2 or 6-keto-PGF1 alpha in guinea pig lung fragments and PGE2 or PGF2 alpha in bovine seminal vesicles, suggesting that it did not inhibit cyclooxygenase. These results show that the antiallergic action of amoxanox is associated, at least in part, with the reduction of leukotrienes due to the inhibition of lipoxygenases.
Saijo
T
T
Makino
H
H
Tamura
S
S
Kuriki
H
H
Ashida
Y
Y
Terao
S
S
Maki
Y
Y
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000188:drug therapy; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D006967:Hypersensitivity / Q000188:drug therapy; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors; D008168:Lung / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis
D000631:Aminopyridines; D006634:Histamine H1 Antagonists; D006893:Hydroxyeicosatetraenoic Acids; D016859:Lipoxygenase Inhibitors; D011453:Prostaglandins; D013189:SRS-A; D015117:5,8,11,14-Eicosatetraynoic Acid; D007975:Leukotriene B4; D000001:Calcimycin; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D013929:Thromboxane B2; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C045742:amlexanox