Oxidative metabolism of the GABAAreceptor antagonistt-butylbicycloortho[3[H]benzoate
- 1 January 1987
- journal article
- research article
- Published by Taylor & Francis in Xenobiotica
- Vol. 17 (9) , 1085-1093
- https://doi.org/10.3109/00498258709044207
Abstract
1. The trioxabicyclooctane ring of t-butylbicycloortho[3H]benzoate (TBOB), (CH3)3CC(CH2O)3CC6H5, is cleaved to yield the 3-oxo-benzoate, (CH3)3CC(CHO)(CH2OH)CH2OC(O)C6H 5, on O-methylene hydroxylation by microsomes from mouse liver or houseflies in the presence of NADPH. 2. The methyl and phenyl substituents are tentatively identified as additional sites of oxidative metabolism. 3. The 3-oxo-benzoate from oxidative cage opening and the bis-(hydroxymethyl)-benzoate, (CH3)3CC(CH2OH)CH2OC(O)C6H 5, from enzymic reduction of the 3-oxobenzoate undergo esteratic hydrolysis to benzoic acid. 4. Metabolites of TBOB excreted by rats and houseflies include the bis-(hydroxymethyl)-benzoate and benzoic and hippuric acids. 5. Metabolic hydroxylation of TBOB at O-methylene, alkyl and aryl substituents may serve as a model for detoxication reactions of related potent GABAA receptor antagonists and insecticides.This publication has 11 references indexed in Scilit:
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