Inhibition of prostaglandin synthetases derived from neuronal and glial cells and rat renal medulla by ortho-, meta- and para-substituted aminophenolic compounds.
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 acetylsalicyclic acid and indomethacin, o-, and p-phenetidine and o-aminophenol were as effective as acetylsalicyclic 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 prostaglandin-synthetases in the CNS than against those in the periphery.
D000082:Acetaminophen / Q000494:pharmacology; D000627:Aminophenols / Q000494:pharmacology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001254:Astrocytoma / Q000201:enzymology*; D002460:Cell Line; D002999:Clone Cells / Q000201:enzymology; D016861:Cyclooxygenase Inhibitors; D007679:Kidney Medulla / Q000201:enzymology*; D008297:Male; D051379:Mice; D009447:Neuroblastoma / Q000201:enzymology*; D010615:Phenacetin / Q000494:pharmacology; D010628:Phenetidine / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D000627:Aminophenols; D016861:Cyclooxygenase Inhibitors; D010628:Phenetidine; D000082:Acetaminophen; D010615:Phenacetin; D001241:Aspirin