N-acetylcyanamide, the major urinary metabolite of cyanamide in rat, rabbit, dog, and man

Shirota, F.N.; Nagasawa, H.T.; Kwon, C.H.; DeMaster, E.G.

Drug Metabolism and Disposition the Biological Fate of Chemicals 12(3): 337-344


ISSN/ISBN: 0090-9556
PMID: 6145561
Document Number: 5533
The structure of the major urinary metabolite of cyanamide, the active component of the alcohol deterrent agents Temposil , Dipsan , and Abstem , in rats, rabbits, and dogs has been established as N- acetylcyanamide by its identity with chemically synthesized N- acetylcyanamide , and by conversion of the metabolite and the synthetic product to identical derivatives, viz. to N-benzyl-N- acetylcyanamide and to N-(p-nitrobenzyl)-N- acetylcyanamide . The latter derivatives were analyzed by pulsed positive/negative ion chemical ionization mass spectroscopy. Urine from patients receiving cyanamide as a treatment mode was shown to contain N- acetylcyanamide by chemical ionization mass spectrometric analysis of the isolated p-nitrobenzyl derivative, thereby establishing that N- acetylcyanamide is also a metabolite in man. The major portion (87%) of the first 27-hr urinary radioactivity excreted by the dog after receiving a low dose of [14C]cyanamide (0.04 mmol/kg, po) was N- acetylcyanamide , as determined by inverse isotope dilution and measurement of the specific radioactivity of its N-p-nitrobenzyl derivative. This indicates that at low doses acetylation is also a major route of biotransformation of cyanamide in the dog. Hepatic N-acetyltransferase, isolated from the rabbit and dog, catalyzed the transfer of the acetyl group from acetyl-S-CoA to [14C]cyanamide producing N-acetyl[14C]cyanamide. The enzyme isolated from the liver of a rapid acetylator phenotype rabbit was twice as effective as the dog enzyme in catalyzing this transfer. Thus, the enzyme responsible for this biotransformation of cyanamide is an acetyl-S-CoA-dependent N-acetyltransferase.

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N-acetylcyanamide, the major urinary metabolite of cyanamide in rat, rabbit, dog, and man