Abstract
The role of cytochrome P-450s (CYPs) inS-mephobarbital N-demethylation was investigated by using human liver microsomes and cDNA-expressed CYPs. Among the 10 cDNA-expressed CYPs studied (CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4), only CYP2B6 could catalyze S-mephobarbitalN-demethylation. The apparentKm values of human liver microsomes forS-mephobarbital N-demethylation were close to that of cDNA-expressed CYP2B6 (about 250 μM). TheN-demethylase activity of S-mephobarbital in 10 human liver microsomes was strongly correlated with immunodetectable CYP2B6 levels (r = 0.920,p < .001). Orphenadrine (300 μM), a CYP2B6 inhibitor, inhibited the N-demethylase activity ofS-mephobarbital in human liver microsomes to 29% of control activity. Therefore, it appears that CYP2B6 mainly catalyzesS-mephobarbital N-demethylation in human liver microsomes.
Footnotes
-
Send reprint requests to: Kaoru Kobayashi, Ph.D., Laboratory of Biochemical Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, Chiba University, Yayoi-cho 1–33, Inage-ku, Chiba 263-8522, Japan. E-mail: kaoruk{at}p.chiba-u.ac.jp
-
↵1 Present address: Laboratory of Biochemical Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, Japan.
- Abbreviation used is::
- CYP
- cytochrome P-450
- Received July 13, 1999.
- Accepted September 3, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|