Archives of Toxicology

, Volume 73, Issue 8–9, pp 473–478 | Cite as

Comparative evaluation of benzodiazepines for control of soman-induced seizures

  • John H. McDonough Jr
  • Joseph McMonagle
  • Tracy Copeland
  • Dean Zoeffel
  • Tsung-Ming Shih
ORGAN TOXICITY AND MECHANISMS

Abstract

This study evaluated the ability of six benzodiazepines to stop seizures produced by exposure to the nerve agent soman. Guinea pigs, previously prepared with electrodes to record electroencephalographic (EEG) activity, were pretreated with pyridostigmine (0.026 mg/kg, i.m.) 30 min before challenge with soman (56 μg/kg, s.c.) and then treated 1 min after soman exposure with atropine (2.0 mg/kg, i.m.) and pralidoxime chloride (2-PAM Cl; 25 mg/kg, i.m.). All animals developed seizures following this treatment. Benzodiazepines (avizafone, clonazepam, diazepam, loprazolam, lorazepam, and midazolam) were given i.m. 5 or 40 min after seizure onset. All benzodiazepines were effective in stopping soman-induced seizures, but there were marked differences between drugs in the rapidity of seizure control. The 50% effective dose (ED50) values and latencies for anticonvulsant effect for a given benzodiazepine were the same at the two times of treatment delay. Midazolam was the most potent and rapidly acting compound at both treatment times. Since rapid seizure control minimizes the chance of brain damage, use of midazolam as an anticonvulsant may lead to improved clinical outcome in the treatment of nerve agent seizures.

Key words Seizure Benzodiazepine Nerve agent Soman Anticonvulsant 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • John H. McDonough Jr
    • 1
  • Joseph McMonagle
    • 1
  • Tracy Copeland
    • 1
  • Dean Zoeffel
    • 1
  • Tsung-Ming Shih
    • 1
  1. 1.Pharmacology Division, US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010-5400, USA Tel.: 410-436-1942; Fax: 410-436-1960US

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