N-acetyl-5-methoxy kynurenamine, a brain metabolite of melatonin, is a potent inhibitor of prostaglandin biosynthesis.
Although the hypothesis that melatonin may act by inhibiting prostaglandin synthesis arose in part from the similar structures of melatonin and indomethacin, melatonin does not share the in vitro efficacy of indomethacin in inhibiting prostaglandin synthesis. One possibility is that a metabolite of melatonin formed within the target cell might inhibit prostaglandin synthesis and in this study we have tested this by examining the action of the two oxidised metabolites, N-formyl-N-acetyl-5-methoxy kynurenamine formed by the action of indole 2,3-dioxygenase and N-acetyl-5-methoxy kynurenamine , formed in the brain by the action of formamidase . This latter compound which has a structure resembling the fenamate inhibitors of PG biosynthesis had a marked and time dependant inhibiting effect in synthesis using bovine and ovine seminal vesicle microsome preparations and measuring the products by using (1-14C) arachidonic acid and by using a specific antiserum for PGE methyl oxime.
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002417:Cattle; D002855:Chromatography, Thin Layer; D016861:Cyclooxygenase Inhibitors; D066298:In Vitro Techniques; D007735:Kynuramine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D008861:Microsomes / Q000201:enzymology; D011427:Propiophenones / Q000494:pharmacology*; D012669:Seminal Vesicles / Q000201:enzymology; D012756:Sheep
D016861:Cyclooxygenase Inhibitors; D011427:Propiophenones; D007735:Kynuramine; C041550:N-acetyl-N-formyl-5-methoxykynurenamine; C032131:N-acetyl-5-methoxy kynurenamine; D008550:Melatonin; D001241:Aspirin