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Using in vitro techniques, the present study demonstrates that CYP2D6, 2C19 and 3A4 are involved in N-demethylation of citalopram (CIT) enantiomers. Human liver microsome incubations performed with specific inhibitors of these three CYP isozymes have shown up to 60% inhibition of demethylcitalopram production. cDNA expressed human cytochrome P-450 3A4, 2C19 and 2D6 isozymes, but not CYP1A2, were identified to be involved in N-demethylation of CIT enantiomers. Kinetics using cDNA expressed CYP2C19 and CYP3A4 show Km values in the same range: 198 [micro] M, 211 [micro] M for CYP2C19 and 169 [micro] M, 163 [micro] M for CYP3A4 for S-and R-CIT demethylation, respectively. In contrast, kinetics using cDNA expressed CYP 2D6 show a Km of 18 [micro] M and 22 [micro] M for S-and R-CIT demethylation, respectively. Nevertheless, kinetics using cDNA expressed CYP2C19 and 3A4 have …