Presence of flavin-containing monooxygenase in rat brain.

Recent interest has centered on the capability of the brain to metabolize xenobiotics and the presence of cytochrome P450 (P450") and associated monooxygenase activity have indicated the importance of drug metabolism in the brain [1-4]. Besides P450, ravin-containing monooxygenase (FMO, EC 1.14.13.8) is also known to catalyse the oxidation of a wide variety of nitrogen-, sulphurand phosphorus-containing drugs, pesticides and industrial chemicals [5, 6]. FMO which is localized in microsomes has been detected in a wide variety of species [5]. In addition to liver, FMO activity has been detected in other organs, namely, lung, adrenal, kidney and thymus [5]. Some of the best known substrates for hepatic and pulmonary FMO are the psychoactive drugs, namely, antipsychotics (e.g. chloropromazine, trifluopromazine) and tricyclic antidepressants (e.g. imipramine, amitryptaline). Since the major site of action of these drugs is the central nervous system, cerebral FMO could play an important role in pharmacological modulation of these drugs in the brain. In view of this, the presence of FMO in the brain was investigated using model substrates like N,N,dimethylaniline (DMA), methimazole (MEM) and thiobenzamide (TB). Metabolism of DMA, MEM and TB by FMO leads to the formation of N,N,dimethylaniline-Noxide, methimazole-S-oxide and thiobenzamide-S-oxide, respectively.