{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:34:45Z","timestamp":1768476885194,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:00:00Z","timestamp":1708473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>BAER\u2010101 (formerly AZD7325) is a selective partial potentiator of \u03b12\/3\u2010containing \u03b3\u2010amino\u2010butyric acid A receptors (GABAARs) and produces minimal sedation and dizziness. Antiseizure effects in models of Dravet and Fragile X Syndromes have been published. BAER\u2010101 has been administered to over 700 healthy human volunteers and patients where it was found to be safe and well tolerated. To test the extent of the antiseizure activity of BAER\u20101010, we tested BAER\u2010101 in the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model, a widely used and translationally relevant model. GAERS rats with recording electrodes bilaterally located over the frontal and parietal cortices were used. Electroencepholographic (EEG) signals in freely moving awake rats were analyzed for spike\u2010wave discharges (SWDs). BAER\u2010101 was administered orally at doses of 0.3\u2013100\u2009mg\/kg and diazepam was used as a positive control using a cross\u2010over protocol with a wash\u2010out period between treatments. The number of SWDs was dose\u2010dependently reduced by BAER\u2010101 with 0.3\u2009mg\/kg being the minimally effective dose (MED). The duration of and total time in SWDs were also reduced by BAER\u2010101. Concentrations of drug in plasma achieved an MED of 10.1\u2009nM, exceeding the K<jats:sub>i<\/jats:sub> for \u03b12 or \u03b13, but 23 times lower than the K<jats:sub>i<\/jats:sub> for \u03b15\u2010GABAARs. No adverse events were observed up to a dose 300\u00d7\u00a0MED. The data support the possibility of antiseizure efficacy without the side effects associated with other GABAAR subtypes. This is the first report of an \u03b12\/3\u2010selective GABA PAM suppressing seizures in the GAERS model. The data encourage proceeding to test BAER\u2010101 in patients with epilepsy.<\/jats:p>","DOI":"10.1002\/ddr.22160","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T07:48:53Z","timestamp":1708501733000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["BAER\u2010101, a selective potentiator of \u03b12\u2010 and \u03b13\u2010containing GABA<sub>A<\/sub> receptors, fully suppresses spontaneous cortical spike\u2010wave discharges in Genetic Absence Epilepsy Rats from Strasbourg (GAERS)"],"prefix":"10.1002","volume":"85","author":[{"given":"Alexandra","family":"MacLean","sequence":"first","affiliation":[{"name":"Avenue Therapeutics  Miami Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy S.","family":"Chappell","sequence":"additional","affiliation":[{"name":"Avenue Therapeutics  Miami Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay","family":"Kranzler","sequence":"additional","affiliation":[{"name":"Avenue Therapeutics  Miami Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexis","family":"Evrard","sequence":"additional","affiliation":[{"name":"SynapCell SAS  Saint Ismier France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugo","family":"Monchal","sequence":"additional","affiliation":[{"name":"SynapCell SAS  Saint Ismier France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinne","family":"Roucard","sequence":"additional","affiliation":[{"name":"SynapCell SAS  Saint Ismier France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,2,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881109354928"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/156802611795371350"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2020.172996"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.108035"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12413"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2058"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2015.05.022"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.118.249250"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13046"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.117.078873"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007271"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05481-1"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2023.109364"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(02)00068-2"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(22)00077-1"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2006.00607.x"},{"key":"e_1_2_9_18_1","first-page":"65","article-title":"Rat models of genetic absence epilepsy: What do EEG spike\u2010wave discharges tell us about drug effects?","volume":"24","author":"Luijtelaar E. 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