Antagonism of soman-induced convulsions by midazolam, diazepam and scopolamine
Autor: | W.J. Lennox, Susan L. Byers, Larrel W. Harris, Benedict R. Capacio, Fat Chun T. Chang, Dana R. Anderson, Wallace B. Baze |
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Rok vydání: | 1997 |
Předmět: |
Male
Health Toxicology and Mutagenesis medicine.medical_treatment Midazolam Scopolamine Soman Convulsants Muscarinic Antagonists Pharmacology Toxicology Rats Sprague-Dawley chemistry.chemical_compound Seizures Convulsion medicine Animals Chemical Warfare Agents Antidote GABA Modulators Chemical Health and Safety Diazepam business.industry Electromyography Public Health Environmental and Occupational Health Brain Electroencephalography General Medicine Rats Atropine chemistry Pyridostigmine Anesthesia Toxicity Anticonvulsants Cholinesterase Inhibitors medicine.symptom business medicine.drug |
Zdroj: | Drug and chemical toxicology. 20(3) |
ISSN: | 0148-0545 |
Popis: | 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. |
Databáze: | OpenAIRE |
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