Reductive metabolism of the anticonvulsant agent zonisamide, a 1,2-benzisoxazole derivative
| Autor: | Robicheau Jt, Stiff Dd, Zemaitis Ma |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Male
Cytochrome Health Toxicology and Mutagenesis Metabolite Zonisamide Pharmacology Toxicology Biochemistry chemistry.chemical_compound Cytochrome P-450 Enzyme System Enterobacteriaceae medicine Animals Humans biology Benzisoxazole Cytochrome P450 Rats Inbred Strains General Medicine Metabolism Isoxazoles biology.organism_classification Rats Intestines Microsoma chemistry Liver biology.protein Microsome Microsomes Liver Oxidation-Reduction NADP medicine.drug Subcellular Fractions |
| Zdroj: | Xenobiotica; the fate of foreign compounds in biological systems. 22(1) |
| ISSN: | 0049-8254 |
| Popis: | 1. The metabolism of zonisamide in vitro was characterized through aerobic and anaerobic incubations with rat liver subcellular fractions and cultured gastrointestinal microflora. 2. Zonisamide reacted with rat hepatic microsomal cytochrome P-450 and exhibited a Type I binding spectrum. 3. Metabolism of zonisamide in vitro by hepatic subcellular fractions and cultured gastrointestinal flora produced a single metabolite, 2-(sulphamoylacetyl)-phenol (2-SMAP), by reductive cleavage of the 1,2-benzisoxazole ring. 4. The reductive metabolism of zonisamide was primarily mediated by microsomal cytochrome P-450. The soluble fraction enhanced reduction when combined with the microsomal fraction but itself possessed only weak reductive activity. 5. Reduction of zonisamide by the most enzymically active liver fractions required NADPH, was stimulated by FMN and SKF-525A, and was inhibited by CO or air, as well as by n-octylamine. 6. Unlike their involvement in the reduction of numerous nitro, azo, and N-oxide compounds, cultured aerobic and anaerobic intestinal flora were not principally involved in the reduction of zonisamide. |
| Databáze: | OpenAIRE |
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