In vitro formation of methyldiethyldithiocarbamate after the reaction of nitrosoacetoxymethylmethylamine or methylnitrosourea with disulfiram.
Analysis by scintillation measurement, mass spectrometry and h.p.l.c. showed that diethyldithiocarbamic acid (DDTC), the main metabolite of disulfiram (DSF), forms methyldithiocarbamate (MeDDTC) when incubated with [14C]nitrosoacetoxymethylmethylamine ([14C]NAMM) or [14C]methylnitrosourea ([14C]MNU) in different media (bacteria, esterases, rat liver 9000 x g supernatant fraction and microsomes). When DSF instead of DDTC was used, MeDDTC was formed only when soluble enzymes were present which are required to split DSF into two DDTC moieties. No physiological methylation of DDTC takes place as was shown by experiments with [3H]MNU. [14C]Methanol, formed by the decay of [14C]NAMM and [14C]MNU was shown to have no alkylating properties.
D000818:Animals; D001711:Biotransformation; D055598:Chemical Phenomena; D002621:Chemistry; D003600:Cytosol / Q000378:metabolism; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives* / Q000378:metabolism; D004221:Disulfiram / Q000378:metabolism*; D004050:Ditiocarb / Q000031:analogs & derivatives / Q000378:metabolism*; D004347:Drug Interactions; D008099:Liver / Q000378:metabolism; D008297:Male; D008770:Methylnitrosourea / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D009607:Nitrosourea Compounds / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013859:Thiocarbamates / Q000378:metabolism*
D009607:Nitrosourea Compounds; D013859:Thiocarbamates; C014659:methyl(acetoxymethyl)nitrosamine; D008770:Methylnitrosourea; C016571:methyl diethyldithiocarbamate; D004050:Ditiocarb; D004128:Dimethylnitrosamine; D004221:Disulfiram