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.
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.
Gordon
W P
WP
Department of Pharmacokinetics/Drug Metabolism, Merrell Dow Research Institute-Indianapolis Center IN 46268-0470.
Cheng
H
H
Larsen
D L
DL
Ragner
J A
JA
Landmesser
N G
NG
D000818:Animals; D004285:Dogs; D008252:Macaca fascicularis; D008297:Male; D012702:Serotonin Antagonists / Q000378:metabolism* / Q000652:urine; D013045:Species Specificity; D014326:Tropanes / Q000378:metabolism* / Q000652:urine
D012702:Serotonin Antagonists; D014326:Tropanes; C042253:bemesetron