Antagonism of soman-induced convulsions by midazolam, diazepam and scopolamine.
The effects of midazolam (MDZ), diazepam (DZ) and scopolamine (SCP) therapies on soman-induced electrocorticogram (ECoG) and biceps femoris electromyogram (EMG) activities and brain lesions were assessed in male rats. Animals received pyridostigmine (26 micrograms/kg, im) 30 min before soman (87.1 micrograms/kg, im) followed by therapy consisting of atropine (1.5 mg/kg) admixed with 2-PAM (25 mg/kg, im) 1 min later; MDZ (0.5 mg/kg), DZ (1.77 mg/kg) or SCP (0.43 mg/kg) was administered im at 1 min after the onset of convulsions (CVs). Typically, within 5 min after soman the ECoG profile changed to a full-blown, spike-and-dome epileptiform (SDE) pattern followed by CVs and increased amplitude of EMG activity. Treatment with SCP restored ECoG and EMG profiles by 30 min. At 2 hr after exposure only 1 animal demonstrated a slight abnormality in ECoG activity which was normal at 24 hr. Similarly, DZ and MDZ restored EcoG and EMG profiles by 30 min; however, in contrast to SCP, 83% of the animals demonstrated reappearance of SDE 2 hrs after soman. SCP therapy also enabled rats to move about in their cages by 30 min post treatment. In contrast, DZ- and MDZ-treated rats remained incapacitated as late as 2 hr post-exposure. Animals were euthanized at 24 hr, and the extent of soman-induced brain lesions was determined by light microscopic analysis. When present, brain lesions were minimal in SCP-treated rats. The mean brain lesion scores across all experimental conditions ranked as follows: soman control > MDZ > DZ > or = SCP = saline control. These observations suggest that SCP may be highly effective in severe soman intoxication.
Anderson
D R
DR
US Army Medical Research Institute of Chemical Defense, Pharmacology Division, Aberdeen Proving Ground, MD 21010-5425, USA.
Harris
L W
LW
Chang
F C
FC
Baze
W B
WB
Capacio
B R
BR
Byers
S L
SL
Lennox
W J
WJ
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D003292:Convulsants / Q000633:toxicity*; D003975:Diazepam / Q000627:therapeutic use; D004569:Electroencephalography; D004576:Electromyography; D018757:GABA Modulators / Q000627:therapeutic use*; D008297:Male; D008874:Midazolam / Q000627:therapeutic use*; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000627:therapeutic use*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D012999:Soman / Q000037:antagonists & inhibitors / Q000633:toxicity*
D000927:Anticonvulsants; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D003292:Convulsants; D018757:GABA Modulators; D018727:Muscarinic Antagonists; D012999:Soman; D012601:Scopolamine; D003975:Diazepam; D008874:Midazolam