{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T01:04:53Z","timestamp":1760403893557,"version":"build-2065373602"},"reference-count":12,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A series of imidazodiazepines has been developed that possess reduced sedative liabilities but retain efficacy in anticonvulsant screening models. The latest of these compounds, (5\u2010(8\u2010ethynyl\u20106\u2010(pyridin\u20102\u2010yl)\u20104H\u2010benzo[<jats:italic>f<\/jats:italic>]imidazole[1,5\u2010\u03b1][1,4]diazepin\u20103\u2010yl) oxazole known as KRM\u2010II\u201081) is currently awaiting advancement into the clinic. A deuterated structural analog (D5\u2010KRM\u2010II\u201081) was made as a potential backup compound and studied here in comparison to KRM\u2010II\u201081. In the present study, both compounds significantly prevented seizures in mice induced by 6\u2009Hz (44\u2009mA) electrical stimulation without significantly altering motoric function on a rotarod after intraperitoneal administration. Both compounds also significantly prevented clonic seizures, tonic seizures, and lethality induced by pentylenetetrazol in mice when given orally. D5\u2010KRM\u2010II\u201081 had a slightly longer duration of action against clonic and tonic seizures than KRM\u2010II\u201081. Oral administration of 100\u2009mg\/kg of either KRM\u2010II\u201081 or D5\u2010KRM\u2010II\u201081 was significantly less disruptive of sensorimotor function in mice than diazepam (5\u2009mg\/kg, p.o.). The present report documents that D5\u2010KRM\u2010II\u201081 represents another in this series of imidazodiazepines with anticonvulsant activity at doses that do not impair sensorimotor function.<\/jats:p>","DOI":"10.1002\/ddr.22042","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T07:41:41Z","timestamp":1675755701000},"page":"601-605","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Comparative anticonvulsant activity of the GABAkine KRM\u2010II\u201081 and a deuterated analog"],"prefix":"10.1002","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8233-9961","authenticated-orcid":false,"given":"Xingjie","family":"Ping","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology Indiana University\/Purdue University  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle J.","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry, Milwaukee Institute of Drug Discovery University of Wisconsin\u2010Milwaukee  Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas M.","family":"Zahn","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry, Milwaukee Institute of Drug Discovery University of Wisconsin\u2010Milwaukee  Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6233-7747","authenticated-orcid":false,"given":"Lalit K.","family":"Golani","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry, Milwaukee Institute of Drug Discovery University of Wisconsin\u2010Milwaukee  Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dishary","family":"Sharmin","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry, Milwaukee Institute of Drug Discovery University of Wisconsin\u2010Milwaukee  Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamal P.","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry, Milwaukee Institute of Drug Discovery University of Wisconsin\u2010Milwaukee  Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sepideh","family":"Revanian","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry, Milwaukee Institute of Drug Discovery University of Wisconsin\u2010Milwaukee  Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prithu","family":"Mondal","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry, Milwaukee Institute of Drug Discovery University of Wisconsin\u2010Milwaukee  Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoming","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology Indiana University\/Purdue University  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1411-1572","authenticated-orcid":false,"given":"Leggy A.","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry, Milwaukee Institute of Drug Discovery University of Wisconsin\u2010Milwaukee  Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rok","family":"Cerne","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology Indiana University\/Purdue University  Indianapolis Indiana USA"},{"name":"Laboratory of Antiepileptic Drug Discovery St. Vincent's Hospital  Indianapolis Indiana USA"},{"name":"Faculty of Medicine University of Ljubljana  Ljubljana Slovenia"},{"name":"RespireRx Pharmaceuticals Inc  Glen Rock New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James M.","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry, Milwaukee Institute of Drug Discovery University of Wisconsin\u2010Milwaukee  Milwaukee Wisconsin USA"},{"name":"RespireRx Pharmaceuticals Inc  Glen Rock New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Branka","family":"Divovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy University of Belgrade  Belgrade Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miroslav M.","family":"Savi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy University of Belgrade  Belgrade Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnold","family":"Lippa","sequence":"additional","affiliation":[{"name":"RespireRx Pharmaceuticals Inc  Glen Rock New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jodi L.","family":"Smith","sequence":"additional","affiliation":[{"name":"Laboratory of Antiepileptic Drug Discovery St. Vincent's Hospital  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9048-148X","authenticated-orcid":false,"given":"Jeffrey M.","family":"Witkin","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; 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