J. Skibba, D. D. Beal, G. Ramirez
1970
Citations
3
Influential Citations
104
Citations
Quality indicators
Journal
Cancer research
Abstract
4(5)-(3,3-Dimethyl-1-triazeno)imidazole-5(4)-carboxamide (DIC) was N -demethylated in vitro by rat liver microsomes resulting in the formation of 20.5 mμmoles of formaldehyde/mg microsomal protein/30 min. 4(5)-Aminoimidazole-5(4)-carboxamide was recovered in vitro as a major metabolic product following N -demethylation resulting in the formation of 14.9 mμmoles/mg microsomal protein/30 min. The administration of 14C-methyl-labeled DIC intraperitoneally to rats was followed by the recovery of 4.0% of the dose as 14CO2 within 6 hr. When 14C-methyl-labeled DIC was administered intraperitoneally to rats pretreated with prochlorperazine or phenobarbital, increased amounts (8.1% and 10.5% respectively) of DIC were N -demethylated to 14CO2 within 6 hr. One patient given 14C-methyl-labeled DIC orally expired 21.4% of the radioactivity as 14CO2 within 6 hr. N -Demethylation appears to be a major metabolic pathway of DIC in rats and man. This reaction is mediated by liver microsomal enzymes that can be induced by barbiturates and perhaps prochlorperazine.