PHOSPHOTRIESTERASE, PRALIDOXIME-2-CHLORIDE (2-PAM) AND EPTASTIGMINE TREATMENTS AND THEIR COMBINATIONS IN DFP INTOXICATION

The protective action of i.v. administered eptastigmine, an organophos phate hydrolase (phosphotriesterase), or pralidoxime-2-chloride (2-PAM ) and their combination in acute diisopropylfluorophosphate (DFP) into xication were evaluated in mice. The mice received the physostigmine d erivative, eptastigmine (0.9 mg/kg body wt, i.v.), 10 min prior to the i.p. injection of DFP (1.8 mg/kg body wt). Phosphotriesterase (66 mu mol/min x ml/g and 6 mu g/g body wt) or 2-PAM (30 mg/kg body wt) were given i.v. 30 min after DFP. The animals also received atropine sc (37 .5 mg/kg body wt) immediately after DFP. The cholinesterase (ChE) acti vities were not protected or reactivated by 2-PAM alone. The ChE activ ities in brain and plasma were protected by phosphotriesterase. Eptast igmine alone assisted the recovery of the brain ChE activities. Also t he combination of eptastigmine-phosphotriesterase protected the brain enzymes. It did not, however, provide any additional protection compar ed with phosphotriesterase-treatment on its own. In brain, the combina tion of eptastigmine with 2-PAM resulted in partly restored enzyme act ivities 24 hr after DFP exposure. In plasma, eptastigmine did not prev ent the inhibition of ChE by DFP. However, when it was combined with p hosphotriesterase, it significantly promoted the recovery of plasma Ch E activity. In lung and in erythrocytes, the various combinations of a ntidotes caused only minor changes in the ChE activities. (C) 1996 Aca demic Press, Inc.