title: Pharmacological dissociation of the motor and electrical aspects of convulsive status epilepticus induced by the cholinesterase inhibitor soman.
abstract: In an effort to validate methods to be used in a screen for drugs effective as anticonvulsants for soman-induced convulsions, scopolamine (0.2 mg/kg) or diazepam (1 mg/kg) were given (i.m.) to male guinea pigs as a pretreatment 30 min before a convulsant dose of soman. Pyridostigmine, atropine and pralidoxime chloride also were given to counteract the lethality of soman. All animals challenged with soman and which did not receive either diazepam or scopolamine exhibited convulsive status epilepticus (SE), identified by continuous electrographic seizure activity (EGSA) and continuous motor convulsions. Despite the presence of continuous motor convulsions in all animals pretreated with diazepam and challenged with soman, EGSA was not observed in five of the seven animals. Continuous motor convulsions developed in four of seven animals pretreated with scopolamine and challenged with soman, but EGSA was not observed in any scopolamine-pretreated guinea pig. Neuronal necrosis was observed in the hippocampus, thalamus, amygdala, and cerebral and pyriform cortices in each animal with EGSA, but not brain damage was found in subjects without EGSA. Thus, although convulsions, EGSA and brain damage normally occur together in animals exposed to soman, the convulsions can be pharmacologically dissociated from the EGSA and brain damage, demonstrating that the clinically manifested convulsions are not dependent on EGSA recorded from the cortex or on abnormal activity which leads to neuronal necrosis in the forebrain.
authors.affiliation: Neurotoxicology Branch, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010.
authors.forename: S
authors.initials: S
authors.lastname: Sparenborg
authors.forename: L H
authors.initials: LH
authors.lastname: Brennecke
authors.forename: E T
authors.initials: ET
authors.lastname: Beers
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001921:Brain / Q000473:pathology; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D003975:Diazepam / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects; D006168:Guinea Pigs; D007091:Image Processing, Computer-Assisted; D008297:Male; D011220:Pralidoxime Compounds / Q000494:pharmacology; D011729:Pyridostigmine Bromide / Q000494:pharmacology; D012601:Scopolamine / Q000494:pharmacology; D012999:Soman / Q000633:toxicity*; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*
chemical_list: D000931:Antidotes; D002800:Cholinesterase Inhibitors; D011220:Pralidoxime Compounds; D001285:Atropine; D012999:Soman; D012601:Scopolamine; D011729:Pyridostigmine Bromide; C028797:pralidoxime; D003975:Diazepam