Xenobiotic and endobiotic inhibitors of cytochrome P-450dbl function, the target of the debrisoquine/sparteine type polymorphism

Biochem Pharmacol. 1988 Oct 15;37(20):3829-35. doi: 10.1016/0006-2952(88)90063-9.


Five to 10% of Caucasians are poor metabolizers (PM) of debrisoquine, sparteine, bufuralol and numerous other drugs. A deficiency in cytochrome P-450dbl (P-450dbl) function is the cause of this polymorphism of drug oxidation with autosomal recessive inheritance. In the present study, inhibition of bufuralol-1'-hydroxylase in human liver microsomes by drugs and chemicals was performed in a search for potential new substrates for this polymorphic enzyme. Among the 80 alkaloids and drugs tested, 25 were competitive inhibitors. In vitro competitive inhibition of bufuralol oxidation by a substance indicates that this compound is able to bind to the same enzymatic site as bufuralol. This may mean that the competing drug also is metabolized by P-450dbl and that its metabolism is subject to the same genetic variation as the oxidation of bufuralol. However, some of these competitive inhibitors are not oxidized by P-450dbl. In this case, however, they may interfere with the in vivo phenotyping procedure by inhibiting the formation of metabolites of test drugs such as debrisoquine, sparteine, metoprolol or dextrometorphan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology
  • Antipsychotic Agents / pharmacology
  • Cytochrome P-450 Enzyme Inhibitors*
  • Cytochrome P-450 Enzyme System
  • Debrisoquin / metabolism*
  • Humans
  • In Vitro Techniques
  • Isoquinolines / metabolism*
  • Mixed Function Oxygenases / antagonists & inhibitors
  • Polymorphism, Genetic*
  • Sparteine / metabolism*
  • Xenobiotics / pharmacology*


  • Alkaloids
  • Antipsychotic Agents
  • Cytochrome P-450 Enzyme Inhibitors
  • Isoquinolines
  • Xenobiotics
  • Sparteine
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • bufuralol 1'-hydroxylase
  • Debrisoquin