Abstract |
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.
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Authors | William L Fitch, Yuan Chen, Liling Liu, Axel Paehler, May Young |
Journal | Drug metabolism letters
(Drug Metab Lett)
Vol. 4
Issue 2
Pg. 77-87
(Apr 2010)
ISSN: 1874-0758 [Electronic] United Arab Emirates |
PMID | 20446913
(Publication Type: Journal Article)
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Chemical References |
- Adrenergic alpha-2 Receptor Antagonists
- Imidazoles
- Cytochrome P-450 Enzyme System
- Imiloxan
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Topics |
- Adrenergic alpha-2 Receptor Antagonists
(analysis, metabolism)
- Animals
- Biotransformation
- Cytochrome P-450 Enzyme System
(metabolism)
- Hepatocytes
(metabolism)
- Humans
- Imidazoles
(analysis, metabolism)
- In Vitro Techniques
- Liver
(metabolism)
- Microsomes, Liver
(metabolism)
- Protein Binding
- Rats
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