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This study evaluated the efficacy of valnoctamide (racemic\u2010VCD), sec<\/jats:italic>\u2010butylpropylacetamide (racemic\u2010SPD), and phenobarbital for stopping nerve agent seizures in both immature and adult rats.<\/jats:p><\/jats:sec>Methods<\/jats:title>Female and male postnatal day (PND<\/jats:styled-content>) 21, 28, and 70 (adult) rats, previously implanted with electroencephalography (EEG) electrodes were exposed to seizure\u2010inducing doses of the nerve agents sarin or VX and EEG<\/jats:styled-content> was recorded continuously. Five minutes after seizure onset, animals were treated with SPD<\/jats:styled-content>, VCD,<\/jats:styled-content> or phenobarbital. The up\u2010down method was used over successive animals to determine the anticonvulsant median effective dose (ED50<\/jats:sub>) of the drugs.<\/jats:p><\/jats:sec>Results<\/jats:title>SPD\u2010ED50<\/jats:sub> values in the VX<\/jats:styled-content> model were the following: PND<\/jats:styled-content>21, 53\u00a0mg\/kg (male) and 48\u00a0mg\/kg (female); PND<\/jats:styled-content>28, 108\u00a0mg\/kg (male) and 43\u00a0mg\/kg (female); and PND<\/jats:styled-content>70, 101\u00a0mg\/kg (male) and 40\u00a0mg\/kg (female). SPD<\/jats:styled-content>\u2010ED<\/jats:styled-content>50<\/jats:sub> values in the sarin model were the following: PND<\/jats:styled-content>21, 44\u00a0mg\/kg (male) and 28\u00a0mg\/kg (female); PND<\/jats:styled-content>28, 79\u00a0mg\/kg (male) and 34\u00a0mg\/kg (female); and PND<\/jats:styled-content>70, 53\u00a0mg\/kg (male) and 53\u00a0mg\/kg (female). VCD<\/jats:styled-content>\u2010ED<\/jats:styled-content>50<\/jats:sub> values in the VX<\/jats:styled-content> model were the following: PND<\/jats:styled-content>21, 34\u00a0mg\/kg (male) and 43\u00a0mg\/kg (female); PND<\/jats:styled-content>28, 165\u00a0mg\/kg (male) and 59\u00a0mg\/kg (female); and PND<\/jats:styled-content>70, 87\u00a0mg\/kg (male) and 91\u00a0mg\/kg (female). VCD<\/jats:styled-content>\u2010ED<\/jats:styled-content>50<\/jats:sub> values in the sarin model were the following: PND<\/jats:styled-content>21, 45\u00a0mg\/kg (male), 48\u00a0mg\/kg (female); PND<\/jats:styled-content>28, 152\u00a0mg\/kg (male) 79\u00a0mg\/kg (female); and PND<\/jats:styled-content>70, 97\u00a0mg\/kg (male) 79\u00a0mg\/kg (female). Phenobarbital\u2010ED<\/jats:styled-content>50<\/jats:sub> values in the VX<\/jats:styled-content> model were the following: PND<\/jats:styled-content>21, 43\u00a0mg\/kg (male) and 18\u00a0mg\/kg (female); PND<\/jats:styled-content>28, 48\u00a0mg\/kg (male) and 97\u00a0mg\/kg (female). Phenobarbital\u2010ED<\/jats:styled-content>50<\/jats:sub> values in the sarin model were the following: PND<\/jats:styled-content>21, 32\u00a0mg\/kg (male) and 32\u00a0mg\/kg (female); PND<\/jats:styled-content>28, 58\u00a0mg\/kg (male) and 97\u00a0mg\/kg (female); and PND<\/jats:styled-content>70, 65\u00a0mg\/kg (female).<\/jats:p><\/jats:sec>Significance<\/jats:title>SPD<\/jats:styled-content> and VCD<\/jats:styled-content> demonstrated anticonvulsant activity in both immature and adult rats in the sarin\u2010 and VX<\/jats:styled-content>\u2010induced status epilepticus<\/jats:styled-content> models. Phenobarbital was effective in immature rats, whereas in adult rats, higher doses were required that were accompanied by toxicity. Overall, significantly less drug was required to stop seizures in PND<\/jats:styled-content>21 animals than in the older animals, and overall, males required higher amounts of drug than females.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.14630","type":"journal-article","created":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T02:16:57Z","timestamp":1547000217000},"page":"315-321","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Comparative efficacy of valnoctamide and sec<\/i>\u2010butylpropylacetamide (SPD<\/scp>) in terminating nerve agent\u2013induced seizures in pediatric rats"],"prefix":"10.1111","volume":"60","author":[{"given":"Kari M.","family":"Haines","sequence":"first","affiliation":[{"name":"Nerve Agent Countermeasures, Medical Toxicology Division US Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liana M.","family":"Matson","sequence":"additional","affiliation":[{"name":"Nerve Agent Countermeasures, Medical Toxicology Division US Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily N.","family":"Dunn","sequence":"additional","affiliation":[{"name":"Nerve Agent Countermeasures, Medical Toxicology Division US Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cherish E.","family":"Ardinger","sequence":"additional","affiliation":[{"name":"Nerve Agent Countermeasures, Medical Toxicology Division US Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn","family":"Lee\u2010Stubbs","sequence":"additional","affiliation":[{"name":"Research Support Division US Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Bibi","sequence":"additional","affiliation":[{"name":"Institute for Drug Research School of Pharmacy Faculty of Medicine The Hebrew University of Jerusalem Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"McDonough","sequence":"additional","affiliation":[{"name":"Nerve Agent Countermeasures, Medical Toxicology Division US Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meir","family":"Bialer","sequence":"additional","affiliation":[{"name":"Institute for Drug Research School of Pharmacy Faculty of Medicine The Hebrew University of Jerusalem Jerusalem Israel"},{"name":"David R. 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