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), 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.
Tuovinen
K
K
Department of Physiology, University of Kuopio, Finland. kai.tuovinen@uku.fi
Hänninen
O
O
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000633:toxicity*; D003292:Convulsants / Q000633:toxicity*; D007928:Lethal Dose 50; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D010830:Physostigmine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012999:Soman / Q000633:toxicity*
D002800:Cholinesterase Inhibitors; D003292:Convulsants; C052450:physostigmine heptyl; D001285:Atropine; D012999:Soman; D010830:Physostigmine