N-methylation of nicotine enantiomers by human liver cytosol

J Pharm Pharmacol. 1988 Feb;40(2):153-4. doi: 10.1111/j.2042-7158.1988.tb05207.x.


Incubation of human liver cytosol with either R-(+)-[3H-N'CH3]nicotine or S-(-)-[3H-N'CH3]nicotine results in the formation of the corresponding N-methyl quaternary ammonium metabolite. A substrate stereoselectivity was observed in that the turnover number for the methylation of the S-(-)-isomer was 0.25 pmol mg-1 protein h-1, whereas that for the R-(+)-isomer was 2.11. The latter substrate exhibited an apparent Km value of 20.1 microM. Nicotine N-methylation appears to be species-dependent, since rat liver homogenates contained no 'nicotine N-methyltransferase' activity, whereas with guinea-pig liver homogenates, a substrate specificity for only R-(+)-nicotine was observed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytosol / metabolism*
  • Guinea Pigs
  • Humans
  • In Vitro Techniques
  • Liver / metabolism*
  • Male
  • Methylation
  • Nicotine / metabolism*
  • Nicotine / pharmacokinetics
  • Rats
  • Stereoisomerism


  • Nicotine