Metabolism of tracazolate. Metabolites in dog and rat urine
Heald, A.F.; Dizio, D.P.; Kirkland, K.M.; Loftus, P.; Malbica, J.O.
Drug Metabolism and Disposition the Biological Fate of Chemicals 14(6): 631-636
1986
ISSN/ISBN: 0090-9556 PMID: 2877818 Document Number: 284911
The urinary metabolites of tracazolate [4-n-butylamino-1-ethyl-6-methyl-1H-pyrazolo (3,4-b) pyridine-5-carboxylic acid ethyl ester], an anxiolytic agent, obtained from rats and dogs dosed with 14C-labeled tracazolate have been characterized. No unchanged tracazolate was detected. Fifteen metabolites were identified in dog urine, seven of which had not previously been found in rat blood and tissue. Eleven of these metabolites were also found in rat urine. The metabolites were formed by 1) deesterification to the 5-carboxylic acid; 2) N-deethylation of the pyrazole ring: 3) oxidation at the .gamma.-position of the n-butylamino side chain; 4) oxidation of the terminal carbon of this side chain; 5) loss of the n-butylamino group; and 6) hydroxylation of the 6-methyl group followed by condensation with the 5-carboxylic acid to form .gamma.-lactones. The major metabolites in dog urine were the desethyl-desbutyl-deesterified compound, the desbutyl-deesterified compound, and the desbutyl-desethyl-lactone. Loss of the butyl side chain and, also, lactone formation, appeared to occur to a lesser extent in the rat than in the dog.