Enantioselective N-oxygenation of chlorpheniramine by the flavin-containing monooxygenase from hog liver

1. The metabolism of racemic, (D)- and (L)-chlorpheniramine, a widely used antihistamine, was studied in microsomes and with highly purified flavin-containing monooxygenase from hog liver. 2. Although some N-demethylation was observed, the major metabolite of chlorpheniramine in hog liver microsomes was the aliphatic nitrogen N-oxide. Chlorpheniramine was extensively N-oxygenated by the highly purified flavin-containing monooxygenase from hog liver. 3. N-Oxygenation of chlorpheniramine in both microsomes and highly purified flavin-containing monooxygenase from hog liver was enantioselective. The Km for (D)-chlorpheniramine N-oxygenation was markedly lower than that for (L)-chlorpheniramine. 4. Molecular modelling studies were performed to investigate the nature of the substrate binding region.