Oxidation diazinon metabolism

The metabolic pathways of diazinon are shown in Figure 8.26. Diazinon is mainly hydrolyzed to diethylthiophosphoric acid by cytochrome P450 monooxygenases and esterase (phosphatase). Diazinon is also oxidized by P450s to diazoxon. Microsomal monooxygenases also oxidize diazinon at the isopropyl group. The methyl group on the pyrimidine... 

Keizer J, G d Agostino, R Nagel, F Gramenzi, L Vittozzi (1993) Comparative diazinon toxicity in guppy and zebra fish different role of oxidative metabolism. Environ Toxicol Chem 12 1243-1250. 

Plant Diaziuou was rapidly absorbed by and translocated in rice plants. Metabolites identified in both rice plants and a paddy soil were 2-isopropyl-4-methyl-6-hydroxypyrimidine (hydrolysis product), 2-(l -hydroxy-l -methyl)ethyl-4-methyl-6-hydroxypyrimidine, and other polar compounds (Laanio et al, 1972). Oxidizes in plants to diazoxon (Laanio et al., 1972 Ralls et al, 1966 Wolfe et al., 1976) although 2-isopropyl-4-methylpyrimidin-6-ol was identified in bean plants (Kansouh and Hopkins, 1968) and as a hydrolysis product in soil (Somasundaram et al., 1991) and water (Suffet et al., 1967). Five d after spraying, pyrimidine ring-labeled C-diazinon was oxidized to oxodiazinon which then hydrolyzed to 2-isopropyl-4-methylpyrimidin-6-ol which, in turn, was further metabolized to carbon dioxide (Ralls et al, 1966). Diazinon was transformed in field-sprayed kale plants to hydroxydiazinon 0,0-diethyl-0-[2-(2 -hydroxy-2 -propyl)-4-methyl-6-pyrimidinyl] phosphorothioate which was not previously reported (Pardue et al., 1970). 

In animals pretreated with ethanol, metabolism of cocaine to norcocaine and benzoylnorecgonine increased, as reflected by higher tissue AUCs, as compared with those receiving water. Ethanol pretreatment also resulted in measurable levels of norcocaethylene in liver and lung. These observations are consistent with the increased hepatotoxicity (presumably due to enhanced N-oxidative metabolism) observed when mice were exposed to cocaine or cocaethylene and the esterase inhibitor diazinon (Roberts et al. 1992 Thompson et al. 1979). This shift toward N-oxidative metabolism provides a mechanism to explain potentiation of cocaine hepatotoxicity by ethanol (lover et al. 1991). Detection of norcocaethylene in ethanol- pretreated rats is consistent with norcocaethylene detected in the hair of heavy cocaine users, suggesting common pathways including hydrolysis, transesterification, and N-demethylation (figure 1) (Cone etal. 1991). 

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