EPTASTIGMINE-PHOSPHOTRIESTERASE COMBINATION IN DFP INTOXICATION

A novel therapy against organophosphate exposure, the combination of a carbamate eptastigmine and an organophosphate hydrolase (phosphotries terase) was studied in mice against diisopropylfluorophosphate (DFP) ( 1.75 mg/kg) exposure. Mice received eptastigmine (0.9 mg/kg; iv) 10 mi n prior to the ip injection of DFP. Phosphotriesterase (83 U/g body we ight) was injected iv 10 min after DFP. Eptastigmine (1.5 mg/kg; iv) i nhibited the acetylcholinesterase activities in brain and erythrocytes for a longer time than physostigmine, Eptastigmine caused only minor changes in the behavior and activity of the animals, whereas physostig mine clearly reduced their activity for about 30 min. The eptastigmine pretreatment clearly supplemented the protective effect of phosphotri esterase against DFP: the plasma butyrylcholinesterase activity was do ubled and the activity recovered faster than in animals treated with p hosphotriesterase alone. In lung, butyrylcholinesterase activity was i nitially lower after eptastigmine- phosphotriesterase than phosphotrie sterase treatment alone, However, the activity returned 24 hr later to normal in eptastigmine-phosphotriesterase-treated groups, With phosph otriesterase only, it recovered only to 75% of the control level. Pres umably eptastigmine, by preventing the binding of DFP to cholinesteras es, caused an elevation of free DFP levels in body fluids and promoted phosphotriesterase hydrolysis of DFP. (C) 1996 Academic Press, Inc.