Haemoprotein-mediated metabolism of enamines and the possible involvement of one-electron oxidations

Xenobiotica. 1995 Jul;25(7):769-75. doi: 10.3109/00498259509061892.


1. Microsomal metabolism of 1-benzylpiperidine (1-BP), its cis-2,6-dimethyl (cis-2,6-DMBP), 4,4-dimethyl (4,4-DMBP), and alpha, alpha-dimethyl (alpha, alpha-DMBP) analogues, and phencyclidine (PCP) has been studied to assess the involvement of P450 oxidation of the enamine tautomers of the initial endocyclic iminium metabolites. 2. The selective prevention by cyanide of the metabolite production of 1-benzyl-3-piperidone but not 1-benzyl-3-piperidinol from 1-BP is consistent with the enamine as the source of the 3-one metabolite. 3. The parent amines and particularly the independently prepared iminium species induced a pattern of metabolism-dependent irreversible inactivation of P450 benz-phetamine demethylase activity, consistent with involvement of enamine C-3 oxidation in the inactivation process. 4. Substrate activity of the endocyclic enamines and alpha-aminoketones (presumably the enol-enamine tautomers) for horseradish peroxidase under conditions where simple aliphatic amines display no activity is consistent with metabolic one-electron oxidations of the enamines.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amines / metabolism*
  • Animals
  • Cations / chemistry
  • Cytochrome P-450 Enzyme System / metabolism
  • Electron Transport
  • Hemeproteins / metabolism*
  • Horseradish Peroxidase / metabolism
  • In Vitro Techniques
  • Male
  • Microsomes, Liver / enzymology
  • Microsomes, Liver / metabolism
  • Oxidation-Reduction
  • Rabbits
  • Stereoisomerism


  • Amines
  • Cations
  • Hemeproteins
  • Cytochrome P-450 Enzyme System
  • Horseradish Peroxidase