The metabolic fate of the dopamine agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin in rats after intravenous and oral administration II. Isolation and identification of metabolites

Abstract

1. The in vivo metabolic pathways of 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (I) in rats have been established, using in vitro metabolism as a complementary technique.

2. All identified metabolites were conjugates. Glucuronidation at the phenolic group yields the major metabolite, accounting for 50% (i.v.) or 65% (oral) of the dose. The corresponding sulphate conjugate of I is virtually absent (less than 0.2% dose).

3. Hydroxylation of I, at the ortho position to the phenolic hydroxy group, yields 6-hydroxy-I (II), accounting for about 13% (i.v.) or 9% (oral) dose. This catechol is excreted, as a glucuronide, almost exclusively into the bile. Both the 5- and the 6-glucuronide of II were detected in about equal amounts.

4. Metabolism of I in vitro showed that under oxidative conditions, depropylation of I occurred. Conjugation of ³H-I in the presence of UDPGA or PAPS, was successful in yielding the glucuronide and sulphate conjugates.