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

FN Shirota, HT Nagasawa, CH Kwon and EG DeMaster

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.

Volume 12, Issue 3, pp. 337-344, 05/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics

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