Effectiveness of procyclidine in combination with carbamate prophylactics against diisopropylfluorophosphate poisoning

Abstract

The protective effect of cholinolytics such as procyclidine and atropine, in combination with carbamate prophylactics, against diisopropylfluorophosphate poisoning was examined in mice. Doses of carbamates were optimized, based on the maximum sign-free dose, the time course of cholinesterase inhibition and the protective potential against diisopropylfluorophosphate poisoning. Centrally-active physostigmine was more toxic than centrally-inactive pyridostigmine and the toxic signs of carbamates appeared to be closely related to the level of inhibition of brain cholinesterase activity. In combination with atropine, physostigmine was more effective than pyridostigmine in protecting mice intoxicated with diisopropylfluorophosphate. Moreover, centrally-active atropine sulfate was a more effective co-antidote to carbamates than centrally-inactive atropine methylnitrate. The most prominent protection was achieved with the combination of carbamates and procyclidine, a centrally-active cholinolytic showing anticonvulsion, which was also observed to prevent diisopropylfluorophosphate-induced convulsions ( Kim et al., 1997). Taken together, it is suggested that procyclidine could be a possible substitute for atropine as an antidote to diisopropylfluorophosphate poisoning.