METABOLISM OF METHOXYPHENAMINE IN-VITRO BY A CYP2D6 MICROSOMAL PREPARATION

Metabolism of methoxyphenamine (MP) was conducted in vitro using comme rcially available microsomes prepared from human AHH-1 TK+/- cells in which CYP2D6 had been expressed. This study has confirmed the involvem ent of CYP2D6 in the metabolism of MP to O-desmethylmethoxyphenamine ( OHMP) and 5-hydroxymethoxyphenamine (5HMP), but not to N-desmethylmeth oxyphenamine. It has also revealed that CYP2D6 catalyzes the formation of another, hitherto unknown, ring-hydroxylated metabolite of MP, iso meric with 5HMP. The analytical procedure used to identify and quantif y MP metabolites involved an acetylation procedure that had distinct a dvantages. MP and its basic and amphoteric metabolites were all conver ted to neutral products that were efficiently extracted into organic s olvent.