Archives of Pharmacal Research
- Volume 18 Issue 6
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- Pages.381-384
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- 1995
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- 0253-6269(pISSN)
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- 1976-3786(eISSN)
In vitro Ccovalent Binding of SC-42867, PGE2 Antagonist, to Rat Liver Microsomal Proteins
Abstract
Covalent binding of the reactive metabolites of SC_42867 to microsomal proteins has been examined. In the absence of inhibitor of cytochrome oxydase (.alpha.-naphtyl-isothiocyanate) or a radical scavenger (3-terthiobuty-4-hydroxyanisol), up to 4.0% of total redioactivity used in the assay could irreversibly bind to proteins. In the presence of an inhibitor, the highest percentage of covalent binding observed is 0.7% a significant decrease of the metabolism of SC42876 was observed. These results suggest in a cytochrome P-450 dependent generation of SC_42867 metabolites significantly take part in the covalent binding process.