{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:07:49Z","timestamp":1790327269326,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,3,23]],"date-time":"2012-03-23T00:00:00Z","timestamp":1332460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold>Midazolam is a short\u2010acting benzodiazepine that is widely used as an i.v. sedative and anticonvulsant. Besides interacting with the benzodiazepine site associated with GABA<jats:sub>A<\/jats:sub>receptors, some benzodiazepines act as agonists of translocator protein (18\u2003kDa) (TSPO) to enhance the synthesis of steroids, including neurosteroids with positive modulatory actions on GABA<jats:sub>A<\/jats:sub>receptors. We sought to determine if neurosteroidogenesis induced by midazolam contributes to its anticonvulsant action.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold>Mice were pretreated with neurosteroid synthesis inhibitors and potentiators followed by midazolam or clonazepam, a weak TSPO ligand. Anticonvulsant activity was assessed with the i.v. pentylenetetrazol (PTZ) threshold test.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold>Midazolam (500\u20135000\u2003\u00b5g\u00b7kg<jats:sup>\u22121<\/jats:sup>, i.p.) caused a dose\u2010dependent increase in seizure threshold. Pretreatment with the neurosteroid synthesis inhibitors finasteride, a 5\u03b1\u2010reductase inhibitor, and a functional TSPO antagonist PK 11195, reduced the anticonvulsant action of midazolam. The anticonvulsant action of midazolam was enhanced by the neurosteroidogenic drug metyrapone, an 11\u03b2\u2010hydroxylase inhibitor. In contrast, the anticonvulsant action of clonazepam (100\u2003\u00b5g\u00b7kg<jats:sup>\u22121<\/jats:sup>) was reduced by finasteride but not by PK 11195, indicating a possible contribution of neurosteroids unrelated to TSPO.<\/jats:p><jats:p><jats:bold>CONCLUSION AND IMPLICATIONS<\/jats:bold>Enhanced endogenous neurosteroid synthesis, possibly mediated by an interaction with TSPO, contributed to the anticonvulsant action of midazolam. Enhanced neurosteroidogenesis may also be a factor in the actions of other benzodiazepines, even those that only weakly interact with TSPO.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01733.x","type":"journal-article","created":{"date-parts":[[2011,10,21]],"date-time":"2011-10-21T11:59:40Z","timestamp":1319198380000},"page":"2684-2691","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Role of neurosteroids in the anticonvulsant activity of midazolam"],"prefix":"10.1111","volume":"165","author":[{"given":"Ashish","family":"Dhir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael 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