{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:07:32Z","timestamp":1790266052890,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,8,12]],"date-time":"2018-08-12T00:00:00Z","timestamp":1534032000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Antiepileptic drugs that modulate GABA have the potential to aggravate or improve the symptoms of absence epilepsy. PF\u201006372865 is a positive allosteric modulator (PAM) of \u03b12\/3\/5 subunit\u2010containing GABA<jats:sub>A<\/jats:sub> receptors with minimal activity at \u03b11\u2010containing receptors, which are believed to mediate many of the adverse events associated with benzodiazepines. The aim of this study was to assess the antiepileptic effect of PF\u201006372865 in a preclinical model of absence seizures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genetic absence epilepsy rats from Strasbourg (GAERS) was implanted with four cortical electrodes over the frontoparietal cortex, and the number and cumulated duration of spike\u2010and\u2010wave discharges (SWDs) were recorded for 10\u201090\u00a0minutes following administration of vehicle, PF\u201006372865, and positive controls diazepam and valproate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PF\u201006372865 (0.3, 1, 2, 10\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>) dose\u2010dependently reduced the expression of SWDs, including full suppression at the highest doses by 30\u00a0minutes after administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>PF\u201006372865 demonstrated robust efficacy in suppressing SWDs in the GAERS model of absence epilepsy. To our knowledge, this is the first demonstration of antiepileptic activity of an \u03b12\/3\/5\u2010subtype\u2010selective GABA<jats:sub>A<\/jats:sub> PAM in a model of absence epilepsy. Further study of the antiepileptic properties of PF\u201006372865 is warranted in patients with absence seizures.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13046","type":"journal-article","created":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T06:03:45Z","timestamp":1534140225000},"page":"255-260","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Pronounced antiepileptic activity of the subtype\u2010selective GABA<sub>A<\/sub>\u2010positive allosteric modulator PF\u201006372865 in the GAERS absence epilepsy model"],"prefix":"10.1111","volume":"25","author":[{"given":"Venceslas","family":"Duveau","sequence":"first","affiliation":[{"name":"SynapCell SAS Saint Ismier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek L.","family":"Buhl","sequence":"additional","affiliation":[{"name":"Neuroscience Research Unit Pfizer Inc Cambridge 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