{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T01:25:01Z","timestamp":1768008301153,"version":"3.49.0"},"reference-count":80,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CounterACT Program, National Institutes of Health, Office of the Directo","award":["5R21NS094131-02"],"award-info":[{"award-number":["5R21NS094131-02"]}]},{"name":"CounterACT Program, National Institutes of Health, Office of the Directo","award":["1U01NS102135-01A1"],"award-info":[{"award-number":["1U01NS102135-01A1"]}]},{"name":"National Institute of Neurologic Disorders and Stroke","award":["5R21NS094131-02"],"award-info":[{"award-number":["5R21NS094131-02"]}]},{"name":"National Institute of Neurologic Disorders and Stroke","award":["1U01NS102135-01A1"],"award-info":[{"award-number":["1U01NS102135-01A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Acute exposure to nerve agents induces status epilepticus (SE), which can cause death or long-term brain damage. Diazepam is approved by the FDA for the treatment of nerve agent-induced SE, and midazolam (MDZ) is currently under consideration to replace diazepam. However, animal studies have raised questions about the neuroprotective efficacy of benzodiazepines. Here, we compared the antiseizure and neuroprotective efficacy of MDZ (5 mg\/kg) with that of tezampanel (LY293558; 10 mg\/kg), an AMPA\/GluK1 receptor antagonist, administered 1 h after injection of the nerve agent, soman (1.2 \u00d7 LD50), in adult male rats. Both of the anticonvulsants promptly stopped SE, with MDZ having a more rapid effect. However, SE reoccurred to a greater extent in the MDZ-treated group, resulting in a significantly longer total duration of SE within 24 h post-exposure compared with the LY293558-treated group. The neuroprotective efficacy of the two drugs was studied in the basolateral amygdala, 30 days post-exposure. Significant neuronal and inter-neuronal loss, reduced ratio of interneurons to the total number of neurons, and reduction in spontaneous inhibitory postsynaptic currents accompanied by increased anxiety were found in the MDZ-treated group. The rats treated with LY293558 did not differ from the control rats (not exposed to soman) in any of these measurements. Thus, LY293558 has significantly greater efficacy than midazolam in protecting against prolonged seizures and brain damage caused by acute nerve agent exposure.<\/jats:p>","DOI":"10.3390\/toxics10080409","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T04:52:47Z","timestamp":1658724767000},"page":"409","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Antiseizure and Neuroprotective Efficacy of Midazolam in Comparison with Tezampanel (LY293558) against Soman-Induced Status Epilepticus"],"prefix":"10.3390","volume":"10","author":[{"given":"Taiza H.","family":"Figueiredo","sequence":"first","affiliation":[{"name":"Department of Anatomy, Physiology, and Genetics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vassiliki","family":"Aroniadou-Anderjaska","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology, and Genetics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"},{"name":"Department of Psychiatry, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volodymyr I.","family":"Pidoplichko","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology, and Genetics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James P.","family":"Apland","sequence":"additional","affiliation":[{"name":"Neuroscience Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Aberdeen, MD 21010, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria F. M.","family":"Braga","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology, and Genetics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"},{"name":"Department of Psychiatry, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"108298","DOI":"10.1016\/j.neuropharm.2020.108298","article-title":"Acetylcholinesterase inhibitors (nerve agents) as weapons of mass destruction: History, mechanisms of action, and medical countermeasures","volume":"181","author":"Apland","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1164\/rccm.201406-1150CI","article-title":"Respiratory complications of organophosphorus nerve agent and insecticide poisoning. Implications for respiratory and critical care","volume":"190","author":"Hulse","year":"2014","journal-title":"Am. J. Respir. Crit. 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