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It is well known that neuronal excitability is related to \u03b3\u2010aminobutyric acid (GABA)ergic depolarization. HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>\u2010dependent depolarization can be suppressed by membrane\u2010permeable inhibitors of carbonic anhydrase. We previously identified some isoquinoline sulfonamides as potent and selective inhibitors of the human carbonic anhydrase\u2005II and VII (hCA\u2005II and hCA\u2005VII) isoforms. Given that hCA\u2005II and hCA\u2005VII are specific isoforms involved in GABA\u2010mediated neuronal excitation, we hypothesized that they could represent the biological target for the development of new anticonvulsant agents. Therefore, for selected isoquinoline sulfonamides, we preliminarily tested their ability to prevent audiogenic seizures in DBA\/2 mice. All compounds were evaluated after intraperitoneal administration, and some of them proved to protect the mice against convulsions. Among this series of compounds, several derivatives showed combined in\u2005vivo efficacy with inhibitory effects toward the targeted carbonic anhydrases (i.e., hCA\u2005II and hCA\u2005VII). Specifically, the most interesting molecule was 1\u2010(4\u2010aminophenyl)\u20106,7\u2010dimethoxy\u20103,4\u2010dihydroisoquinoline\u20102(1<jats:italic>H<\/jats:italic>)\u2010sulfonamide (<jats:bold>6<\/jats:bold>), which proved to be a more active and selective hCA\u2005VII inhibitor than the reference compound topiramate. Further studies to explore the in\u2005vivo pharmacokinetic profile of the most active compounds may help to provide insight into the future design of selective hCA\u2005VII inhibitors.<\/jats:p>","DOI":"10.1002\/cmdc.201500596","type":"journal-article","created":{"date-parts":[[2016,2,26]],"date-time":"2016-02-26T02:41:10Z","timestamp":1456454470000},"page":"1812-1818","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["In\u2005Vivo Evaluation of Selective Carbonic Anhydrase Inhibitors as Potential Anticonvulsant Agents"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5192-448X","authenticated-orcid":false,"given":"Elvira","family":"Bruno","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences (CHIBIOFARAM) University of Messina  Viale Annunziata 98168 Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3704-0076","authenticated-orcid":false,"given":"Maria R.","family":"Buemi","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences (CHIBIOFARAM) University of Messina  Viale Annunziata 98168 Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0614-5713","authenticated-orcid":false,"given":"Laura","family":"De\u2005Luca","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences (CHIBIOFARAM) University of Messina  Viale Annunziata 98168 Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0841-9626","authenticated-orcid":false,"given":"Stefania","family":"Ferro","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences (CHIBIOFARAM) University of Messina  Viale Annunziata 98168 Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3149-9639","authenticated-orcid":false,"given":"Anna\u2010Maria","family":"Monforte","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences (CHIBIOFARAM) University of Messina  Viale Annunziata 98168 Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4262-0323","authenticated-orcid":false,"given":"Claudiu T.","family":"Supuran","sequence":"additional","affiliation":[{"name":"Neurofarba: Department of Neuroscience, Psychology, Pharmaceuticals and Child Health Section of Pharmaceutical and Nutraceutical Sciences University of Florence  50019 Sesto Fiorentino Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1352-1900","authenticated-orcid":false,"given":"Daniela","family":"Vullo","sequence":"additional","affiliation":[{"name":"Neurofarba: Department of Neuroscience, Psychology, Pharmaceuticals and Child Health Section of Pharmaceutical and Nutraceutical Sciences University of Florence  50019 Sesto Fiorentino Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7629-6579","authenticated-orcid":false,"given":"Giovambattista","family":"De\u2005Sarro","sequence":"additional","affiliation":[{"name":"Science of Health Department, School of Medicine University of Catanzaro  Viale Europa Localit\u00e0 Germaneto 88100 Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1279-8123","authenticated-orcid":false,"given":"Emilio","family":"Russo","sequence":"additional","affiliation":[{"name":"Science of Health Department, School of Medicine University of Catanzaro  Viale Europa Localit\u00e0 Germaneto 88100 Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0002-2253","authenticated-orcid":false,"given":"Rosaria","family":"Gitto","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences (CHIBIOFARAM) University of Messina  Viale Annunziata 98168 Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,24]]},"reference":[{"key":"e_1_2_6_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1734-1140(13)71060-0"},{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2006.11.010"},{"key":"e_1_2_6_3_1","first-page":"7","volume":"48","author":"Rogawski M. 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