Prophylactic Detoxification by Physostigmine and Procyclidine of Diisopropylfluorophosphate Poisoning

The antidotal, anticonvulsant and neuroprotective effects of physostigmine and procyclidine. the combinational prophylactics for organophosphate poisoning, were evaluated in rats. In comparison with a low protective effect (1.6 fold) of atropine (15 mg/kg) and 2-pralidoxime (30 mg/kg), the traditional antidotes regimen, a marked protection ratio of 7.3 fold was achieved by combinational pretreatment with physostigmine (0.05 mg/kg) and procyclidine (10 mg/kg), which was superior to that (3.5 fold) with pyri-dostigmine (0.1 mg/kg) and atropine (15 mg/kg). Rats exposed to a high dose (10 mg/kg. 2 X <TEX>$LD_{50}$</TEX>) of diisopropylfluorophosphate showed severe epileptiform seizures on electroencephalography, resulting in necrotic and apoptotic brain injuries in discrete brain regions under histopathological and TUNEL immuno-histochemical examinations in 24 hr. Such seizures and excitotoxic brain injuries were fully prevented by pretreatment with physostigmine (0.05 mg/kg) and procyclidine (10 mg/kg). in contrast to a negligible effect of pyridostigmine (0.1 mg/kg) and atropine (15 mg/kg). Taken together, it is proposed that the prophylactics composed of physostigmine and procyclidine could be a promising regimen for the prevention of lethality, seizures and brain injuries induced by organophosphate poisoning.