Inhibitory actions of desacetylation products of phenacetin and paracetamol on prostaglandin synthetases in neuronal and glial cell lines and rat renal medulla

The inhibitory actions of phenacetin and paracetamol and of their desacetylation products on prostaglandin synthesis were studied on enzyme preparations originating from a neuronal cell line (mouse neuroblastoma, clone N2A), a glial cell line (rat astrocytoma, clone C6) and rat renal medulla. All compounds tested inhibited cultured cell and kidney prostaglandin synthetases to similar extents. p-Phenetidin and p-aminophenol, the desacetylated metabolites of phenacetin and paracetamol, were either 7–10 times or 4 times more potent than paracetamol. Thus, p-phenetidin inhibited prostaglandin synthesis as efficaciously as did acetylsalicylic acid. The possible roles of p-phenetidin as the active metabolite of phenacetin for cyclo-oxygenase inhibition in brain and of phenacetin as an organ pro-drug are discussed.