{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:51:08Z","timestamp":1785131468542,"version":"3.55.0"},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,7,20]],"date-time":"2017-07-20T00:00:00Z","timestamp":1500508800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Na<jats:sub>v<\/jats:sub>1.1 (<jats:italic><jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content>1A<\/jats:italic>) channels primarily located in gamma\u2010aminobutyric acid (<jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content>)ergic fast\u2010spiking interneurons are pivotal for action potential generation and propagation in these neurons. Inappropriate function of fast\u2010spiking interneurons, leading to disinhibition of pyramidal cells and network desynchronization, correlates with decreased cognitive capability. Further, reduced functionality of Na<jats:sub>v<\/jats:sub>1.1 channels is linked to various diseases in the central nervous system. There is, at present, however no subtype selective pharmacological activators of Na<jats:sub>v<\/jats:sub>1.1 channels available for studying pharmacological modulation of interneuron function. In the current study, we identified a small molecule Na<jats:sub>v<\/jats:sub>1.1 activator, 3\u2010amino\u20105\u2010(4\u2010methoxyphenyl)thiophene\u20102\u2010carboxamide, named <jats:styled-content style=\"fixed-case\">AA<\/jats:styled-content>43279, and provided an <jats:italic>in\u00a0vitro<\/jats:italic> to <jats:italic>in\u00a0vivo<\/jats:italic> characterization of the compound. In <jats:styled-content style=\"fixed-case\">HEK<\/jats:styled-content>\u2010293 cells expressing human Na<jats:sub>v<\/jats:sub>1.1 channels, <jats:styled-content style=\"fixed-case\">AA<\/jats:styled-content>43279 increased the Na<jats:sub>v<\/jats:sub>1.1\u2010mediated current in a concentration\u2010dependent manner mainly by impairing the fast inactivation kinetics of the channels. In rat hippocampal brain slices, <jats:styled-content style=\"fixed-case\">AA<\/jats:styled-content>43279 increased the firing activity of parvalbumin\u2010expressing, fast\u2010spiking <jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content>ergic interneurons and increased the spontaneous inhibitory post\u2010synaptic currents (<jats:styled-content style=\"fixed-case\">sIPSC<\/jats:styled-content>s) recorded from pyramidal neurons. When tested <jats:italic>in\u00a0vivo<\/jats:italic>,<jats:styled-content style=\"fixed-case\"> AA<\/jats:styled-content>43279 had anti\u2010convulsive properties in the maximal electroshock\u00a0seizure\u00a0threshold test. <jats:styled-content style=\"fixed-case\">AA<\/jats:styled-content>43279 was tested for off\u2010target effects on 72 different proteins, including Na<jats:sub>v<\/jats:sub>1.2, Na<jats:sub>v<\/jats:sub>1.4, Na<jats:sub>v<\/jats:sub>1.5, Na<jats:sub>v<\/jats:sub>1.6 and Na<jats:sub>v<\/jats:sub>1.7 and exhibited reasonable selectivity. Taken together, <jats:styled-content style=\"fixed-case\">AA<\/jats:styled-content>43279 might constitute a valuable tool compound for revealing biological functions of Na<jats:sub>v<\/jats:sub>1.1 channels.<\/jats:p>","DOI":"10.1111\/ejn.13626","type":"journal-article","created":{"date-parts":[[2017,6,21]],"date-time":"2017-06-21T08:22:41Z","timestamp":1498033361000},"page":"1887-1896","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["A small molecule activator of Na<sub>v<\/sub>1.1 channels increases fast\u2010spiking interneuron excitability and GABAergic transmission <i>in\u00a0vitro<\/i> and has anti\u2010convulsive effects <i>in\u00a0vivo<\/i>"],"prefix":"10.1111","volume":"46","author":[{"given":"Kristen","family":"Frederiksen","sequence":"first","affiliation":[{"name":"Neuroscience Drug Discovery H. 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