A Study on the Anticonvulsant Effects of Centrally-Acting Drugs by Measuring Electroencephalography of Experimental Animals Intoxicated with Organophosphate Compounds

Abstract

Organophosphorus compounds are irreversible inhibitors of cholinesterase enzyme. Exposure causes a progression of toxic signs, including hypersecretion, tremor, convulsion, respiratory distress, epileptiform seizure, brain injuries and death. To protect brain injuries, administration of diazepam as a neuroprotectant is now considered essential for severely exposed nerve agent casualties. However, studies have shown diazepam to provide less than total protection against the neuropathological consequences of nerve agent exposure. In this context, extensive studies have been carried out to find out effective alternative drugs to protect brain from epileptiform seizures induced by organophosphate compounds intoxication. It has been reported that a combination of carbamate and anticholinergic or antiglutamatergic can be a very effective medical countermeasure in dealing with the threat of organophosphorous poisoning. In this study, experimental animals including rats and guinea pigs were implanted with microelectrodes on their brain sculls, and treated with various centrally acting drugs such as physostigmine and procyclidine prior to soman challenge, and then its electroencephalography(ECoG) was monitored to see anticonvulsant effects of the drugs. It was found that seizure activities in ECoG were not always in proportion to clinical signs induced by soman intoxication, and that combinative pretreatment with physostigmine plus procyclidine effectively stopped the seizures induced by organophosphorous poisoning.