{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:20:04Z","timestamp":1787023204185,"version":"build-2736575974"},"reference-count":54,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GE 1103\/9\u20101"],"award-info":[{"award-number":["GE 1103\/9\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      An attractive target to interfere with epileptic brain hyperexcitability is the enhancement of \u03b3\u2010aminobutyric acidergic (GABAergic) inhibition by inactivation of the GABA\u2010metabolizing enzyme GABA aminotransferase (GABA\u2010AT). GABA\u2010AT inactivators were designed to control seizures by raising brain GABA levels. OV329, a novel drug candidate for the treatment of epilepsy and addiction, has been shown\n                      <jats:italic>in vitro<\/jats:italic>\n                      to be substantially more potent as a GABA\u2010AT inactivator than vigabatrin, an antiseizure drug approved as an add\u2010on therapy for adult patients with refractory complex partial seizures and monotherapy for pediatric patients with infantile spasms. Thus, we hypothesized that OV329 should produce pronounced anticonvulsant effects in two different rat seizure models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We therefore examined the effects of OV329 (5, 20, and 40\u00a0mg\/kg ip) on the seizure threshold of female Wistar Unilever rats, using the timed intravenous pentylenetetrazole (ivPTZ) seizure threshold model as a seizure test particularly sensitive to GABA\u2010potentiating manipulations, and amygdala\u2010kindled rats as a model of difficult\u2010to\u2010treat temporal lobe epilepsy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GABA\u2010AT inactivation by OV329 clearly increased the threshold of both ivPTZ\u2010induced and amygdala\u2010kindled seizures. OV329 further showed a 30\u2010fold greater anticonvulsant potency on ivPTZ\u2010induced myoclonic jerks and clonic seizures compared to vigabatrin investigated previously. Notably, all rats were responsive to OV329 in both seizure models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>These results reveal an anticonvulsant profile of OV329 that appears to be superior in both potency and efficacy to vigabatrin and highlight OV329 as a highly promising candidate for the treatment of seizures and pharmacoresistant epilepsies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.17090","type":"journal-article","created":{"date-parts":[[2021,10,9]],"date-time":"2021-10-09T07:03:12Z","timestamp":1633762992000},"page":"3091-3104","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["OV329, a novel highly potent \u03b3\u2010aminobutyric acid aminotransferase inactivator, induces pronounced anticonvulsant effects in the pentylenetetrazole seizure threshold test and in amygdala\u2010kindled rats"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8670-5495","authenticated-orcid":false,"given":"Malte","family":"Feja","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Toxicology, and Pharmacy University of Veterinary Medicine Hannover Hannover Germany"},{"name":"Center for Systems Neuroscience Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Meller","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology, and Pharmacy University of Veterinary Medicine Hannover Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lillian S.","family":"Deking","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology, and Pharmacy University of Veterinary Medicine Hannover Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Kaczmarek","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology, and Pharmacy University of Veterinary Medicine Hannover Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"During","sequence":"additional","affiliation":[{"name":"Ovid Therapeutics New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B.","family":"Silverman","sequence":"additional","affiliation":[{"name":"Department of Chemistry Department of Molecular Biosciences Chemistry of Life Processes Institute Northwestern University Evanston Illinois USA"},{"name":"Department of Pharmacology Chemistry of Life Processes Institute Northwestern University Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6980-2640","authenticated-orcid":false,"given":"Manuela","family":"Gernert","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology, and Pharmacy University of Veterinary Medicine Hannover Hannover Germany"},{"name":"Center for Systems Neuroscience Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2019.107790"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14596"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.107966"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.8b00009"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410400613"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.84.7.788"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1017589301855"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0920-1211(88)90025-3"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1992.tb00465.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/11317650-000000000-00000"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01988.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm201650r"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebcr.2016.08.002"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b10965"},{"key":"e_1_2_8_16_1","first-page":"1811","volume-title":"I. 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