title: N-acetylcyanamide, the major urinary metabolite of cyanamide in rat, rabbit, dog, and man.
abstract: 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.
mesh_terms: D000107:Acetylation; D000818:Animals; D001711:Biotransformation; D002384:Catalysis; D003484:Cyanamide / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000652:urine; D003486:Cyanides / Q000378:metabolism*; D004285:Dogs; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D013058:Mass Spectrometry; D011817:Rabbits; D051381:Rats; D013045:Species Specificity
chemical_list: D003486:Cyanides; D003484:Cyanamide; C041915:N-acetylcyanamide