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We compared the antiseizure efficacy of midazolam, a current standard of care treatment for OP\u2010induced SE, versus combined therapy with midazolam and allopregnanolone (ALLO) in a rat model of soman\u2010induced SE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Soman\u2010intoxicated male rats with robust seizure behavior and high\u2010amplitude electroencephalographic (EEG) activity were administered midazolam (0.65\u2009mg, i.m.) 20 min after seizure initiation and 10\u2009min later either a second dose of midazolam or ALLO (12 or 24\u2009mg\/kg, i.m.). Seizure behavior and EEG were monitored for 4\u2009h after treatment. Brains were collected at the end of the monitoring period for histological analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Animals receiving 2 doses of midazolam exhibited persistent SE. Sequential dosing with midazolam followed by ALLO suppressed electrographic seizure activity. The combination therapy also significantly reduced soman\u2010induced neurodegeneration and neuroinflammation compared to 2 doses of midazolam. High but not low dose ALLO was associated with transitory and reversible respiratory compromise during the 1\u2009h period after dosing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Treatment with midazolam followed by ALLO was more effective than 2 doses of midazolam in suppressing benzodiazepine\u2010refractory, soman\u2010induced SE, and in mitigating its acute neuropathological consequences.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70215","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T11:45:51Z","timestamp":1741088751000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Allopregnanolone as an Adjunct Therapy to Midazolam is More Effective Than Midazolam Alone in Suppressing Soman\u2010Induced Status Epilepticus in Male Rats"],"prefix":"10.1111","volume":"31","author":[{"given":"Peter 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