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

Drug Metabolism and Pharmacokinetics, Roche Palo Alto LLC, Palo Alto, CA 94304, USA. .
Drug metabolism letters 04/2010; 4(2):77-87. DOI: 10.2174/187231210791292753
Source: PubMed


Imiloxan is an alpha(2) 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.

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