Metabolism of thymoxamine: identification of metabolites in rat
Feniou, C.; Neau, B.; Prat, G.; Cheze, C.; Fauran, F.; Roquebert, J.
Journal of Pharmacy and Pharmacology 32(2): 104-107
1980
ISSN/ISBN: 0022-3573 PMID: 6103028 Document Number: 164645
Thymoxamine hydrochloride [4[(2-dimethylamino)ethoxy]-2-methyl-5-(1-methyl-ethyl) phenol acetate, an autonomic drug], administered by mouth to rats at 25 or 100 mg/kg, was excreted in the urine as the deacetyl and N-demethyl-deacetyl metabolites. These were completely sulfo- and glucuronoconjugated at 25 mg/kg but only partially so at the higher dose. Thymoxamine deacetylation in vitro is catalyzed by plasma and hepatic cytosol esterases and the deacetyl metabolite undergoes N-demethylation catalyzed by the cytochrome P-450 hepatic microsome mixed-function monooxygenase system. The rapidity of the deacetylation suggests that thymoxamine is a prodrug leading in vivo to the active deacetyl thymoxamine.