Application of Modern Drug Metabolism Structure Determination Tools and Assays to the In Vitro Metabolism of Imiloxan

Title: Application of Modern Drug Metabolism Structure Determination Tools and Assays to the In Vitro Metabolism of Imiloxan

Volume: 4 Issue: 2

Author(s): William L. Fitch, Yuan Chen, Liling Liu, Axel Paehler and May Young

Affiliation:

Keywords: Imiloxan, metabolism, mass spectrometry, reactive metabolite

Abstract: Imiloxan is an alpha2 adrenoceptor antagonist and was developed for depression in the 1980s. In Phase 1 clinical trials imiloxan dosing led to hypersensitivity reactions; the molecules 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.

Cite this article as:

L. Fitch William, Chen Yuan, Liu Liling, Paehler Axel and Young May, Application of Modern Drug Metabolism Structure Determination Tools and Assays to the In Vitro Metabolism of Imiloxan, Drug Metabolism Letters 2010; 4 (2) . https://dx.doi.org/10.2174/187231210791292753