The metabolic fate of [¹⁴C]oxaprotiline · HCl in man. II. Isolation and identification of metabolites

Abstract

1. The new antidepressant agent oxaprotiline is extensively metabolized by man. Following an oral 50 mg dose of racemic [¹⁴C]oxaprotiline, most of the ¹⁴C was excreted in the urine as metabolites (>98% total ¹⁴C); only 1% was excreted unchanged.

2. Glucuronidation at the carbinol group of the molecule is the major metabolic pathway (83%). The two diastereoisomeric glucuronides were separated; the more polar O-glucuronide of S(+)-oxaprotiline predominates (44%), suggesting stereoselective disposition of the two enantiomers.

3. Oxidative pathways are minor, and yield desmethyl oxaprotiline (10%) and 3-hydroxy R(—)-oxaprotiline (4%), both of which are conjugated with glucuronic acid.

4. The biotransformation of oxaprotiline in man is less complex than that of other polycyclic antidepressants, which are metabolized mainly by oxidative reactions.