FLAVIN-CONTAINING MONOOXYGENASE MEDIATED METABOLISM OF BENZYDAMINE INPERFUSED BRAIN AND LIVER

Benzydamine (BZY) N-oxidation mediated by flavin-containing monooxygen ase (FMO) was evaluated in perfused brain and liver. Following 20 min of perfusion with modified Ringer solution, the infusion of BZY into b rain or liver led to production of BZY N-oxide. BZY N-oxide, a metabol ite of BZY oxidized exclusively by FMO, was mostly recovered in the ef fluent without undergoing further metabolism or reduction back to the parent substrate. The BZY N-oxide formation rate increased as the infu sion concentration of BZY increased both in perfused brain and perfuse d liver. BZY N-oxidation activities in perfused rat brain and liver we re 4.2 nmol/g brain/min and 50 nmol/g liver/min, respectively, althoug h the BZY N-oxidation activity in brain homogenates was one 4000th tha t in liver homogenates. This is the first study of FMO activity in bra in in situ. (C) 1998 Elsevier Science B.V. All rights reserved.