The role of carboxylesterases in therapeutic interventions of nerve agent poisoning

Abstract Carboxylesterases (CarbE) represent an important factor in studying the new antidotes against G-agents, tabun, sarin, and especially soman. Its isoenzymes exist in many mammalian tissues, but the most important is blood, as it is a medium for transportation of nerve agents to the target organs, such as the central nervous system and respiratory muscles. Rodent species used extensively in such research contain high plasma CarbE activity (mice, rats) or medium level (guinea pigs). At the same time, a low level of plasma CarbE activity was found in marmosets and there was practically no such activity in the plasma of rhesus monkeys and humans. In order to obtain results that would be easily extrapolated to humans, either nonhuman primates with naturally minimal plasma CarbE activity or rodents pretreated with CarbE inhibitors (TOCP, CBDP) should be utilized. In such animals, the LD50 of nerve agents is very similar, as is the efficacy of the prophylactic/postexposure antidotes. CarbEs are also potential stoichiometric scavengers of nerve agents and can be used intravenously to bind organophosphorus compound molecules.