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Table of Contents
Vol. 6, No. 2, 1999
Issue release date: March–April 1999
Section title: Original Paper
J Biomed Sci 1999;6:86–96
(DOI:10.1159/000025375)

Anticonvulsants for Soman-Induced Seizure Activity1

Shih T.-M. · McDonough Jr. J.H. · Koplovitz I.
Pharmacology and Drug Assessment Divisions, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Md., USA

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: 3/19/1999

Number of Print Pages: 11
Number of Figures: 0
Number of Tables: 4

ISSN: 1021-7770 (Print)
eISSN: 1423-0127 (Online)

For additional information: http://www.karger.com/JBS

Abstract

This report describes studies of anticonvulsants for the organophosphorus (OP) nerve agent soman: a basic research effort to understand how different pharmacological classes of compounds influence the expression of seizure produced by soman in rats, and a drug screening effort to determine whether clinically useful antiepileptics can modulate soman-induced seizures in rats. Electroencephalographic (EEG) recordings were used in these studies. Basic studies were conducted in rats pretreated with HI-6 and challenged with 1.6 × LD50 soman. Antimuscarinic compounds were extremely effective in blocking (pretreatment) or terminating soman seizures when given 5 min after seizure onset. However, significantly higher doses were required when treatment was delayed for more than 10 min, and some antimuscarinic compounds lost anticonvulsant efficacy when treatment was delayed for more than 40 min. Diazepam blocked seizure onset, yet seizures could recur after an initial period of anticonvulsant effect at doses ≤2.5 mg/kg. Diazepam could terminate ongoing seizures when given 5 min after seizure onset, but doses up to 20 mg/kg were ineffective when treatment was delayed for 40 min. The GABA uptake inhibitor, tiagabine, was ineffective in blocking or terminating soman motor convulsions or seizures. The glutamate receptor antagonists, NBQX, GYKI 52466, and memantine, had weak or minimal antiseizure activity, even at doses that virtually eliminated signs of motor convulsions. The antinicotinic, mecamylamine, was ineffective in blocking or stopping seizure activity. Pretreatment with a narrow range of doses of α2-adrenergic agonist, clonidine, produced variable protection (40–60%) against seizure onset; treatment after seizure onset with clonidine was not effective. Screening studies in rats, using HI-6 pretreatment, showed that benzodiazepines (diazepam, midazolam and lorazepam) were quite effective when given 5 min after seizure onset, but lost their efficacy when given 40 min after onset. The barbiturate, pentobarbital, was modestly effective in terminating seizures when given 5 or 40 min after seizure onset, while other clinically effective antiepileptic drugs, trimethadione and valproic acid, were only slightly effective when given 5 min after onset. In contrast, phenytoin, carbamazepine, ethosuximide, magnesium sulfate, lamotrigine, primidone, felbamate, acetazolamide, and ketamine were ineffective.


  

Author Contacts

Commander, US Army Medical Research Institute of Chemical Defense
ATTN:MCMR-UV-PN (Dr. T.-M. Shih)
3100 Ricketts Point Rd.
Aberdeen Proving Ground, MD 21010-5400 (USA)
Tel. +1 410 436 3414, Fax +1 410 436 1960, E-Mail dr.tony.shih@amedd.army.mil

  

Article Information

Received: Received: September 22, 1998
Accepted: November 11, 1998
Number of Print Pages : 11
Number of Figures : 0, Number of Tables : 4, Number of References : 52

  

Publication Details

Journal of Biomedical Science (Sponsored by the National Science Council, Taipei)

Vol. 6, No. 2, Year 1999 (Cover Date: March-April 1999)

Journal Editor: Chuan C. Chang, Taipei
ISSN: 1021–7770 (print), 1423–0127 (Online)

For additional information: http://www.karger.com/journals/jbs


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: 3/19/1999

Number of Print Pages: 11
Number of Figures: 0
Number of Tables: 4

ISSN: 1021-7770 (Print)
eISSN: 1423-0127 (Online)

For additional information: http://www.karger.com/JBS


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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