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

Abstract

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 chlorph-eniramine 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 K_m 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.