Metabolism of 4-benzamido-1-[4-(indol-3-yl)-4-oxobutyl]piperidine in rats and monkeys.

R A Franklin, K Heatherington, B Morrison, T Ward

Xenobiotica; the fate of foreign compounds in biological systems 1981 Mar

filter terms:

1. Studies on the absorption, biotransformation and excretion of the potential anti-hypertensive agent 4-benzamido-1-[4-(indol-3-yl)-4-oxobutyl]piperidine (Wy 23699) have been carried out in monkeys and rats. 2. Absorption of the drug in both species was good, as shown by the relative proportions of radioactivity found in the urine after i.v. and oral dosage. 3. Biotransformation was extensive in both species, but the major routes of metabolism were different. In monkey N-dealkylation gave rise to 4-benzamidopiperidine as the principal metabolite; two other minor metabolites were identified as 2-oxo-4-benzamidopiperidine and 4-benzamido-1-[4-(5-hydroxyindol-3-yl)-4-oxo-butyl]piperidine. In the rat, this latter compound (as its conjugate) was the major metabolite; small amounts of benzamidopiperidine but not 2-oxobenzamidopiperidine were found. 4. There was a marked species difference in the route of excretion. Monkeys excreted greater than 60% dose of the drug in the urine, while rats excreted only 19% by this route. This may reflect the species difference in routes of metabolism, metabolic scission of the drug molecule seen in the monkey favouring renal rather than biliary excretion. The toxicological consequences of this are discussed.

Citation

R A Franklin, K Heatherington, B Morrison, T Ward. Metabolism of 4-benzamido-1-[4-(indol-3-yl)-4-oxobutyl]piperidine in rats and monkeys. Xenobiotica; the fate of foreign compounds in biological systems. 1981 Mar;11(3):159-65