{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T05:05:46Z","timestamp":1773291946637,"version":"3.50.1"},"reference-count":46,"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":1430,"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":[[2005,3]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Block of the human two\u2010pore domain potassium (2\u2010PK) channel TREK\u20101 by fluoxetine (Prozac<jats:sup>R<\/jats:sup>) and its active metabolite, norfluoxetine, was investigated using whole\u2010cell patch\u2010clamp recording of currents through recombinant channels in tsA 201 cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Fluoxetine produced a concentration\u2010dependent inhibition of TREK\u20101 current that was reversible on wash. The IC<jats:sub>50<\/jats:sub> for block was 19\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>. Block by fluoxetine was voltage\u2010independent. Fluoxetine (100\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>) produced an 84% inhibition of TREK\u20101 currents, but only a 31% block of currents through a related 2\u2010PK channel, TASK\u20103.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Norfluoxetine was a more potent inhibitor of TREK\u20101 currents with an IC<jats:sub>50<\/jats:sub> of 9\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>. Block by norfluoxetine was also voltage\u2010independent.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Truncation of the C\u2010terminus of TREK\u20101 (\u039489) resulted in a loss of channel function, which could be restored by intracellular acidification or the mutation E306A. The mutation E306A alone increased basal TREK\u20101 current and resulted in a loss of the slow phase of TREK\u20101 activation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Progressive deletion of the C\u2010terminus of TREK\u20101 had no effect on the inhibition of the channel by fluoxetine. The E306A mutation, on the other hand, reduced the magnitude of fluoxetine inhibition, with 100\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc> producing only a 40% inhibition.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>It is concluded that fluoxetine and norfluoxetine are potent inhibitors of TREK\u20101. Block of TREK\u20101 by fluoxetine may have important consequences when the drug is used clinically in the treatment of depression.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2005) <jats:bold>144<\/jats:bold>, 821\u2013829. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706068\">10.1038\/sj.bjp.0706068<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0706068","type":"journal-article","created":{"date-parts":[[2005,2,1]],"date-time":"2005-02-01T09:33:13Z","timestamp":1107250393000},"page":"821-829","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":178,"title":["Inhibition of the human two\u2010pore domain potassium channel, TREK\u20101, by fluoxetine and its metabolite norfluoxetine"],"prefix":"10.1111","volume":"144","author":[{"given":"Louise E","family":"Kennard","sequence":"first","affiliation":[]},{"given":"Justin R","family":"Chumbley","sequence":"additional","affiliation":[]},{"given":"Kishani M","family":"Ranatunga","sequence":"additional","affiliation":[]},{"given":"Stephanie J","family":"Armstrong","sequence":"additional","affiliation":[]},{"given":"Emma L","family":"Veale","sequence":"additional","affiliation":[]},{"given":"Alistair","family":"Mathie","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"S83","article-title":"Potassium channels, in Guide to receptors and channels","volume":"141","author":"ALEXANDER S.P.H.","year":"2004","journal-title":"Br. 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