Flavin-containing monooxygenase mediated metabolism of psychoactive drugs by human brain microsomes.
Flavin-containing monooxygenases (FMO) catalyze the oxidation of certain xenobiotics and drugs which contain a nucleophilic heteroatom. Here we report the first assessment of human brain flavin-containing monooxygenase from tissues obtained at autopsy from seven traffic accident victims. Human brain microsomes catalyzed the S-oxidation or N-oxidation of model substrates methimazole and N,N-dimethylaniline, respectively. The psychoactive drugs chlorpromazine, imipramine and fluoxetine, were also metabolized by human brain FMO. 'Western' immunoblot analyses revealed immunological cross-reactivity of the human brain FMO with rabbit pulmonary FMO. Immunocytochemistry further revealed the localization of the FMO predominantly in the neuronal cell bodies in the magnocellular reticular nuclei, colliculi and substantia nigra. Human brain clearly contains an active FMO system, and it is conceivable that such enzyme(s) are significantly involved in the local metabolism and modulation of pharmacological effects of psychoactive drugs.
Bhamre
S
S
Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, India.
Bhagwat
S V
SV
Shankar
S K
SK
Boyd
M R
MR
Ravindranath
V
V
D000328:Adult; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D002102:Cadaver; D003429:Cross Reactions; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008861:Microsomes / Q000378:metabolism*; D008875:Middle Aged; D010105:Oxygenases / Q000502:physiology*; D011619:Psychotropic Drugs / Q000378:metabolism*; D011817:Rabbits; D014018:Tissue Distribution
D011619:Psychotropic Drugs; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)