In vitro deacetylation studies of acetamidophenolic compounds in rat brain, liver and kidney.
The in vitro deacetylation of ortho-, meta- and para-substituted acetophenetidines and acetamidophenols including acetanilide by arylacylamidases in rat brain, liver and kidney was investigated. In general, deacetylation rates were highest in liver and kidney preparations, whereas brain exhibited lower enzyme activities. Acetophenetidines were more suitable N-deacetylation substrates in comparison to acetamidophenols, whereby o-substituted compounds were split more easily than their corresponding m- or p-analogues. Among the arylacylamides tested, o-acetophenetidine was the predominant substrate in all tissues. It was deacetylated by far more rapidly than phenacetin. The enzymic deacetylation of acetophenetidines in kidney and brain was inhibited by p-nitrophenylacetate revealing that N-acetylamides as well as O-acetyl esters undergo similar degradation by carboxylesterase-amidases. The organophosphorous diester bis(p-nitrophenyl)-phosphate which is known to be a rather selective inhibitor of acetanilide-cleaving hydrolases in rat liver suppressed the deacetylation of acetanilide in all tissues investigated. In contrast to acetanilide, the deacetylation of acetophenetidines was inhibited by bis(p-nitrophenyl)-phosphate in liver and kidney, but bis(p-nitrophenyl)-phosphate was by far less active against acetophenetidine hydrolases in brain.
D000081:Acetamides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003640:Dealkylation; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010615:Phenacetin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000081:Acetamides; D010615:Phenacetin