Involvement of a Cytochrome P4502D Subfamily in Human Liver Microsomal Bunitrolol 4-Hydroxylation

Shizuo Narimatsu, Yasuhiro Masubuchi, Shin Hosokawa, Tokuji Suzuki

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


The oxidative metabolism of bunitrolol, an adrenergic β-receptor antagonist was examined in human liver microsomes fortified with an NADPH-generating system. The microsomal fractions (n=11) showed bunitrolol 4-hydroxylase activities, which correlated well with CYP2D6 contents (correlation coefficient, r = 0.854), debrisoquine 4-hydroxylase (r = 0.953) and imipramine 2-hydroxylase (r = 0.976) activities. On the other hand, the bunitrolol 4-hydroxylase activity showed relatively poor correlations with CYP3A4 content (r = 0.552) and testosterone 6β-Miydroxylase activity (r = 0.668). The bunitrolol 4-hydroxylase activity was significantly inhibited by quinidine, a selective inhibitor for CYP2D6. Polyclonal antibodies raised against rat liver microsomal cytochrome P450BTL, which is thought to belong to the CYP2D subfamily, effectively inhibited bunitrolol 4-hydroxylation. In contrast, polyclonal antibodies raised against human liver microsomal CYP3A4 did not show any inhibitory effect on the activity. These results suggest that CYP2D6 is involved in the bunitrolol 4-hydroxylase activity in human liver microsomes.

Original languageEnglish
Pages (from-to)803-807
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Issue number6
Publication statusPublished - 1994


  • CYP2D6
  • bunitrolol 4-hydroxylation
  • human liver microsome
  • imipramine 2-hydroxylation
  • quinidine

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science


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