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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Metabolism and disposition of the dopamine agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin in conscious monkeys after subsequent i.v. oral, and ocular administration.

The metabolism of 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437) was investigated in conscious monkeys after subsequent i.v., oral, and ocular administration. The administration of the drug caused some physiological effects, such as bradycardia and sedation of the monkeys. During a collection period of 120 hr, on average 83% was recovered after iv administration and 90% after p.o. dosing. After i.v. administration, 44% was excreted in the bile, as compared to 38% in the urine and about 1% in the feces. After oral administration, bile is the major excretion route, accounting for about 60% of the dose, as compared to 25% in the urine and about 5% in the feces. After ocular administration, on average 62% was recovered after 7 hr, excreted in bile and urine in about equal amounts. All percentages given above reflect the total amount of radioactivity recovered, thus comprising the unchanged drug plus various metabolites. After all three dosing routes, N-0437 was metabolized almost completely prior to elimination. Direct glucuronidation of the phenolic group proved to be the major metabolic pathway of N-0437, comprising about 44% of the dose after i.v. and ocular administration and 72% after oral dosing. Hydroxylation of N-0437 at the position ortho to the phenolic group present yielded a catechol intermediate, which was excreted as a glucuronide and accounted for about 10% of the dose. In the monkey, a clear regioselective preference towards glucuronidation at the 6-position was observed. Besides the glucuronide, the sulfoconjugate of N-0437 was a major metabolite after i.v. and ocular administration, accounting for about 15% of the dose.(ABSTRACT TRUNCATED AT 250 WORDS)[1]


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