The metabolism of tetralin

Abstract

1. [1−14C]Tetralin was synthesized and fed to rabbits. 2. Of the radioactivity, 87–90% was excreted in the urine within two days and 0·5–3·7% on the third day. The faeces contained 0·6–1·8%. No radioactivity was found in the breath and negligible amounts were retained in the tissues. About 90–99% of an administered dose was accounted for. 3. The main metabolite in the urine was the glucuronide of α-tetralol (52·4%). Other conjugated metabolites were β-tetralol (25·3%), 4-hydroxy-α-tetralone (6·1%), cis-tetralin-1,2-diol (0·4%) and trans-tetralin-1,2-diol (0·6%). 4. β-Tetralone, α-naphthol, 1,2-dihydronaphthalene and naphthalene, previously reported as metabolites, are artifacts, and tetralin, α-tetralone, β-naphthol, 5-hydroxytetralin, and 6-hydroxytetralin are not metabolites. 5. The major metabolite of tetralin, α-tetralol and α-tetralone is the glucuronide of α-tetralol, which was isolated as methyl (1,2,3,4-tetrahydro-1-naphthyl tri-O-acetyl-β-d-glucosid)uronate; the major metabolite of β-tetralol and β-tetralone is the glucuronide of β-tetralol, which was characterized as methyl (1,2,3,4-tetrahydro-2-naphthyl tri-O-acetyl-β-d-glucosid)uronate. 5-Hydroxytetralin is conjugated with glucuronic acid, and was characterized as methyl (5,6,7,8-tetrahydro-1-naphthyl tri-O-acetyl-β-d-glucosid)uronate. 6-Hydroxytetralin is conjugated with glucuronic acid, and was characterized as methyl (5,6,7,8-tetrahydro-2-naphthyl tri-O-acetyl-β-d-glucosid)uronate. 6. A metabolic sequence accounting for the observed biological transformation products is proposed.