Protection of mice against soman by pretreatment with eptastigmine and physostigmine

Organophosphate (OP) compounds such as the nerve agents sarin, soman and VX are powerful inhibitors of acetylcholinesterases (AChEs), butyrylcholinest erases (BChEs), and carboxylesterases (CaEs) The acute toxicity of OPs is t he result of their irreversible binding with AChEs in the nervous system, w hich elevates the acetylcholine (ACh) levels. In this study the protective actions of intravenously (i.v.), administered eptastigmine and physostigmin e in acute soman intoxication were studied in mice. The mice received eptas tigmine (0.9 mg/kg body weight) or physostigmine (0.1 mg/kg body weight) 10 min prior to the intraperitoneal (i.p.) administration of soman. To avoid possible signs of poisoning, the animals received atropine 37.5 mg/kg body weight subcutaneously (s.c.) in saline immediately after soman injection. E ptastigmine was the most effective carbamate against soman intoxication. Th e LD50 value of soman was 0.44 mg/kg, and the protective ratios of eptastig mine and physostigmine were 2.1- and 1.3-fold, respectively. Both eptastigm ine and physostigmine had protected AChEs when measured 24 h after soman ex posure. In this study, there was no inhibition of microsomal CaEs in soman treated mice. Nonetheless, the role of microsomal CaEs might be more import ant with prophylaxis at multiple LD50s of soman. In conclusion, these resul ts indicate that eptastigmine treatment given i.v. protects better than phy sostigmine against soman exposure. (C) 1999 Elsevier Science Ireland Ltd. A ll rights reserved.