{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T14:08:16Z","timestamp":1761487696669,"version":"3.32.0"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":820,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2006,11]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>Mutations in neuronal K<jats:sub>v<\/jats:sub>7 (KCNQ) potassium channels can cause episodic neurological disorders. Paroxysmal dyskinesias with dystonia are a group of movement disorders which are regarded as ion channelopathies, but the role of K<jats:sub>v<\/jats:sub>7 channels in the pathogenesis and as targets for the treatment have so far not been examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>In the present study, we therefore examined the effects of the activators of neuronal K<jats:sub>v<\/jats:sub>7.2\/7.3 channels retigabine (5, 7.5, 10\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>i.p. and 10, 20\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>p.o.) and flupirtine (10, 20\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>i.p.) and of the channel blocker 10,10\u2010bis(4\u2010pyridinylmethyl)\u20109(10H)\u2010anthracenone (XE\u2010991, 3 and 6\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>i.p.) in the<jats:italic>dt<\/jats:italic><jats:sup><jats:italic>sz<\/jats:italic><\/jats:sup>mutant hamster, a model of paroxysmal dyskinesia in which dystonic episodes occur in response to stress.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>Retigabine (10\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>i.p., 20\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>p.o.) and flupirtine (20\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>i.p.) significantly improved dystonia, while XE\u2010991 caused a significant aggravation in the<jats:italic>dt<\/jats:italic><jats:sup><jats:italic>sz<\/jats:italic><\/jats:sup>mutant. The antidystonic effect of retigabine (10\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>i.p.) was counteracted by XE\u2010991 (3\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>i.p.).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications:<\/jats:title><jats:p>These data indicate that dysfunctions of neuronal K<jats:sub>v<\/jats:sub>7 channels deserve attention in dyskinesias. Since retigabine and flupirtine are well tolerated in humans, the present finding of pronounced antidystonic efficacy in the<jats:italic>dt<\/jats:italic><jats:sup><jats:italic>sz<\/jats:italic><\/jats:sup>mutant suggests that neuronal K<jats:sub>v<\/jats:sub>7 channel activators are interesting candidates for the treatment of dystonia\u2010associated dyskinesias and probably of other types of dystonias. The established analgesic effects of K<jats:sub>v<\/jats:sub>7 channel openers might contribute to improvement of these disorders which are often accompanied by painful muscle spasms.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic>(2006)<jats:bold>149<\/jats:bold>, 747\u2013753. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706878\">10.1038\/sj.bjp.0706878<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1038\/sj.bjp.0706878","type":"journal-article","created":{"date-parts":[[2006,10,3]],"date-time":"2006-10-03T11:10:04Z","timestamp":1159873804000},"page":"747-753","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Antidystonic effects of K<sub>v<\/sub>7 (KCNQ) channel openers in the<i>dt<\/i><sup><i>sz<\/i><\/sup>mutant, an animal model of primary paroxysmal dystonia"],"prefix":"10.1111","volume":"149","author":[{"given":"A","family":"Richter","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S E","family":"Sander","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Rundfeldt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20520"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-3458.2005.tb00033.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(02)02924-2"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4512-03.2004"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-004-0881-1"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1585"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.50.5_Suppl_5.S1"},{"key":"e_1_2_8_9_1","first-page":"93","article-title":"Retigabine (ASTA Medica)","volume":"4","author":"Fatope MO","year":"2001","journal-title":"Drugs"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-18-07052.2000"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870130322"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2001.042suppl.3036.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.04.100"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.jnen.0000178447.79713.bb"},{"key":"e_1_2_8_15_1","first-page":"266","article-title":"Long\u2010term tolerance of flupirtine. 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