Distribution of [3H]diisopropylfluorophosphate, [3H]soman, [3H]sarin, and their metabolites in mouse brain.

The brain area distribution of [3H]diisopropylfluorophosphate, [3H]soman, and [3H]sarin and their metabolites in mice was studied after iv administration of sublethal doses. At the appropriate time after the injection of the radiolabeled organophosphate, the mice were decapitated and their brains were dissected into seven areas. There was a relatively even distribution of the parent compounds and their metabolites in all brain areas except the hypothalamus, which contained concentrations of parent compounds the metabolites that were 2-5 times greater than those in other brain areas. Concentrations of the parent compounds and free metabolites declined steadily throughout the time course, whereas concentrations of the bound metabolites remained relatively constant between 6 and 24 hr. There was no correlation between the disposition of soman, and its metabolites, and cholinesterase inhibition in brain areas, which implicates other central mechanisms in the production of organophosphate effects. However, the higher concentrations of organophosphates and their metabolites in the hypothalamus suggest that this area might be important with respect to the pharmacological effects or the toxicity of these compounds.