{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T02:03:01Z","timestamp":1782007381395,"version":"3.54.5"},"reference-count":34,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,11,6]],"date-time":"2014-11-06T00:00:00Z","timestamp":1415232000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Israel Ministry of Defense, Medicine Branch","award":["039-4489 and 039-4576"],"award-info":[{"award-number":["039-4489 and 039-4576"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Organophosphates (OPs) are commonly used insecticides for agriculture and domestic purposes, but may also serve as nerve agents. Exposure to OPs result in overstimulation of the cholinergic system and lead to status epilepticus (SE), a life\u2010threatening condition that is often resistant to treatment. SE is associated with significant neuronal damage, neurocognitive dysfunction, and the development of lifelong epilepsy. Therefore, rapid termination of SE and prevention of brain damage is of high interest. Here we tested the efficacy of <jats:italic>sec<\/jats:italic>\u2010butyl\u2010propylacetamide (SPD) and two of its individual stereoisomers, (2S,3S)\u2010SPD and (2R,3R)\u2010SPD, in discontinuing OP\u2010induced seizures. SPD is a one carbon homolog of valnoctamide, a central nervous system (CNS)\u2013active constitutional isomer of valproic acid (VPA) corresponding amide valpromide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Rats were implanted with epidural telemetric electrodes to allow electrocorticography (ECoG) recording 24\u00a0h prior, during and 24\u00a0h after poisoning with the OP paraoxon (at a dose equivalent to 1.4 LD<jats:sub>50<\/jats:sub> Median lethal dose). All rats were provided with antidotal treatment of atropine and toxogonin. Epileptic activity was measured using a novel automated system to evaluate the different effects of midazolam, SPD, and its individual stereoisomers in comparison to nontreated controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment with SPD or its individual stereoisomer (2S,3S)\u2010SPD significantly shorten paraoxon\u2010induced SE and reduced the duration of recorded pathologic activity after SE was terminated. (2S,3S)\u2010SPD was superior to racemic\u2010SPD in diminishing delayed pathologic epileptiform activity within the first 8\u00a0h after SE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>These results suggest SPD as an efficient drug for the rapid termination of SE and pathological epileptiform activity following OP poisoning, a strategy to reduce neuronal dysfunction and the risk for lifelong epilepsy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12838","type":"journal-article","created":{"date-parts":[[2014,11,6]],"date-time":"2014-11-06T18:43:04Z","timestamp":1415299384000},"page":"1953-1958","source":"Crossref","is-referenced-by-count":23,"title":["<i>sec\u2010<\/i>Butyl\u2010propylacetamide (SPD) and two of its stereoisomers rapidly terminate paraoxon\u2010induced status epilepticus in rats"],"prefix":"10.1111","volume":"55","author":[{"given":"Guy","family":"Bar\u2010Klein","sequence":"first","affiliation":[{"name":"Departments of Physiology &amp; Cell Biology, Cognitive and Brain Sciences The Zlotowski Center for Neuroscience Ben\u2010Gurion University of the Negev Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evyatar","family":"Swissa","sequence":"additional","affiliation":[{"name":"Departments of Physiology &amp; Cell Biology, Cognitive and Brain Sciences The Zlotowski Center for Neuroscience Ben\u2010Gurion University of the Negev Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyn","family":"Kamintsky","sequence":"additional","affiliation":[{"name":"Departments of Physiology &amp; Cell Biology, Cognitive and Brain Sciences The Zlotowski Center for Neuroscience Ben\u2010Gurion University of the Negev Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tawfeeq","family":"Shekh\u2010Ahmad","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Institute for Drug Research School of Pharmacy Hebrew University Ein Karem Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rotem","family":"Saar\u2010Ashkenazy","sequence":"additional","affiliation":[{"name":"Departments of Physiology &amp; Cell Biology, Cognitive and Brain Sciences The Zlotowski Center for Neuroscience Ben\u2010Gurion University of the Negev Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yechiel","family":"Hubary","sequence":"additional","affiliation":[{"name":"NBC Protection Division IMOD Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shai","family":"Shrot","sequence":"additional","affiliation":[{"name":"Medical Corps Headquarters IDF Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liran","family":"Stetlander","sequence":"additional","affiliation":[{"name":"Medical Corps Headquarters IDF Tel Aviv 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