Studies on the Biodisposition of Organophosphates in Mice

摘要

The time course of (3H) sarin and its metabolites was studied in all of the major organs of the mouse following i.v. administration of sarin. This organophosphate was either rapidly hydrolyzed or it phosphorylated tissue while only trace quantities of intact sarin were found in tissues. Examination of the time course of sarin-induced motor hypoactivity and hypothermia revealed an immediate onset of action which lasted at least 7 hr. However, substantial quantities of radioactivity remained in the brain following recovery of the pharmacological effects. The pharmacological effects of tabun were also evaluated and found to be closely related to those of sarin, the primary difference being tabun was less potent. The biodisposition of fluorophosphate, sarin, and soman, as well their metabolites, was studied in all major areas of the mouse brain. The concentrations of all of these organophosphates were significantly higher in hypothalamus, which suggests an important site of action. Keywords: Soman; Sarin; Tabun; Tissue disposition; Anticholinesterase activity; Behavioral effects. (KT)