Inhibition of prostaglandin synthetases derived from neuronal and glial cells and rat renal medulla by ortho-, meta- and para-substituted aminophenolic compounds

Abstract

Acetophenetidines, acetamidophenols, phenetidines and aminophenols substituted in o-, m- or p-position inhibit prostaglandin-synthetases originating from C 1300 mouse neuroblastoma cells (clone N2A), rat astrocytoma cells (clone C 6) and rat renal medulla. Desacetylated compounds were more potent inhibitors than their corresponding acetyl derivatives and many o- and m-analogues were more active than p-substituted structures like paracetamol (p-acetamidophenol) or phenacetin (p-acetophenetidine). When twelve o-, m- or p-aminophenolic test compounds were compared to acetylsalicylic acid and indomethacin, o-, and p-phenetidine and o-aminophenol were as effective as acetylsalicylic acid. All aminophenol derivatives which inhibited prostaglandin synthesis suppressed cultured nervous cell and kidney cyclo-oxygenases to similar extents. Our results suggest that aminophenolic drugs are not more effective against pros taglandin-synthetases in the CNS than against those in the periphery.