Organophosphate (OP) compounds such as the
nerve agents sarin,
soman and
VX are powerful inhibitors of acetylcholinesterases (
AChEs), butyrylcholinesterases (BChEs), and
carboxylesterases (CaEs) The acute toxicity of OPs is the result of their irreversible binding with
AChEs in the nervous system, which elevates the
acetylcholine (ACh) levels. In this study the protective actions of intravenously (i.v.), administered
eptastigmine and
physostigmine in acute
soman intoxication were studied in mice. The mice received
eptastigmine (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.
Eptastigmine was the most effective
carbamate against
soman intoxication. The LD50 value of
soman was 0.44 mg/kg, and the protective ratios of
eptastigmine and
physostigmine were 2.1- and 1.3-fold, respectively. Both
eptastigmine and
physostigmine had protected
AChEs when measured 24 h after
soman exposure. In this study, there was no inhibition of microsomal CaEs in
soman treated mice. Nonetheless, the role of microsomal CaEs might be more important with prophylaxis at multiple LD50s of
soman. In conclusion, these results indicate that
eptastigmine treatment given i.v. protects better than
physostigmine against
soman exposure.