Application of modern drug metabolism structure determination tools and assays to the in vitro metabolism of imiloxan

Drug Metab Lett. 2010 Apr;4(2):77-87. doi: 10.2174/187231210791292753.


Imiloxan is an alpha2 adrenoceptor antagonist and was developed for depression in the 1980's. In Phase 1 clinical trials imiloxan dosing led to hypersensitivity reactions; the molecule's development was discontinued. The present study revisits the in vitro metabolism of imiloxan using modern analytical methods. Human and rat liver microsomes convert imiloxan into a variety of metabolites many of which are unstable and or reactive. Imiloxan also yields high protein covalent binding in microsomal assays. Imiloxan is a useful test molecule for defining the relationship between liver covalent binding and idiosyncratic toxicity.

MeSH terms

  • Adrenergic alpha-2 Receptor Antagonists / analysis*
  • Adrenergic alpha-2 Receptor Antagonists / metabolism*
  • Animals
  • Biotransformation
  • Cytochrome P-450 Enzyme System / metabolism
  • Hepatocytes / metabolism
  • Humans
  • Imidazoles / analysis*
  • Imidazoles / metabolism*
  • In Vitro Techniques
  • Liver / metabolism
  • Microsomes, Liver / metabolism
  • Protein Binding
  • Rats


  • Adrenergic alpha-2 Receptor Antagonists
  • Imidazoles
  • Cytochrome P-450 Enzyme System
  • Imiloxan