Identification of urinary metabolites of 8-methyl-8-azabicyclo-[3,2,1] octan-3-yl 3,5-dichlorobenzoate (MDL 72,222) in the dog and monkey

Drug Metab Dispos. 1992 Jul-Aug;20(4):596-602.

Abstract

The metabolism of 8-methyl-8-azabicyclo- 3,2,1]octan-3-yl 3,5-dichlorobenzoate (MDL 72,222) was studied in the dog and monkey. Four urinary metabolites were detected by HPLC, HPLC/MS, and GC/MS, and were identified by comparison to authentic standards. The major metabolite in the dog, approximately 41% of the administered dose excreted between 0 and 120 hr, was the MDL 72,222-N-oxide. On the other hand, the major metabolite in the monkey was the glycine conjugate of 3,5-dichlorobenzoic acid (greater than 56% of the dose). Seven percent of the dose in the monkey urine was free 3,5-dichlorobenzoic acid. N-Desmethyl MDL 72,222 was present at 2.5 and 1% in the dog and monkey, respectively. Very little (less than 1%) of the parent compound was found in urine. The major pathways of metabolism of MDL 72,222 are N-oxidation, N-demethylation, ester hydrolysis, and amino acid conjugation.

MeSH terms

  • Animals
  • Dogs
  • Macaca fascicularis
  • Male
  • Serotonin Antagonists / metabolism*
  • Serotonin Antagonists / urine
  • Species Specificity
  • Tropanes / metabolism*
  • Tropanes / urine

Substances

  • Serotonin Antagonists
  • Tropanes
  • bemesetron