{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T02:05:16Z","timestamp":1767665116899},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,2,10]],"date-time":"2009-02-10T00:00:00Z","timestamp":1234224000000},"content-version":"vor","delay-in-days":3754,"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":[[1998,11]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Prolongation of the QT interval and malignant ventricular arrhythmia have been observed in patients administered terodiline for urinary incontinence. Since this adverse reaction might be caused by inhibition of delayed\u2010rectifier K<jats:sup>+<\/jats:sup> current (<jats:italic>I<\/jats:italic><jats:sub>K<\/jats:sub>), we investigated whether clinically relevant (10\u2003\u03bc<jats:sc>m<\/jats:sc>) concentrations of the drug modify <jats:italic>I<\/jats:italic><jats:sub>K<\/jats:sub> in guinea\u2010pig ventricular myocytes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Myocytes superfused with normal Tyrode's solution were pulsed from \u221240\u2003mV to more positive test potentials (<jats:italic>V<\/jats:italic>) for 0.2\u20131\u2003s to elicit tail <jats:italic>I<\/jats:italic><jats:sub>K<\/jats:sub> on repolarization and measure tail <jats:italic>I<\/jats:italic><jats:sub>K<\/jats:sub>\u2010<jats:italic>V<\/jats:italic> relationships. <jats:italic>I<\/jats:italic><jats:sub>Kr<\/jats:sub> was distinguished from <jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub> by its sensitivity to the selective blocker E4031.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Inhibition of <jats:italic>I<\/jats:italic><jats:sub>Kr<\/jats:sub> by 5\u2003\u03bc<jats:sc>m<\/jats:sc> E4031 was completely occluded by pretreatment with 3\u2003\u03bc<jats:sc>m<\/jats:sc> terodiline. In addition, action potential lengthening by E4031 in guinea\u2010pig papillary muscles (29\u00b13%) was abolished (3\u00b12%) (<jats:styled-content><jats:italic>P<\/jats:italic> &lt; 0.001<\/jats:styled-content>) by terodiline pretreatment.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Inhibition of <jats:italic>I<\/jats:italic><jats:sub>Kr<\/jats:sub> by terodiline appeared to be voltage\u2010independent, and the parameters of the Hill equation describing the inhibition were IC<jats:sub>50<\/jats:sub>=0.7\u2003\u03bc<jats:sc>m<\/jats:sc> and <jats:italic>n<\/jats:italic><jats:sub>H<\/jats:sub>=1.6. High concentrations of the drug also affect <jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub>; in experiments with K<jats:sup>+<\/jats:sup>\u2010free Tyrode's, 10\u2003\u03bc<jats:sc>m<\/jats:sc> terodiline inhibited tail <jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub> by 27\u00b13% (<jats:styled-content><jats:italic>n<\/jats:italic> = 5<\/jats:styled-content>) (<jats:styled-content><jats:italic>P<\/jats:italic> &lt; 0.001<\/jats:styled-content>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These data suggest that QT lengthening at therapeutic concentrations of the drug (\u2248amp;1.5\u2003\u03bc<jats:sc>m<\/jats:sc>) is primarily due to inhibition of <jats:italic>I<\/jats:italic><jats:sub>Kr<\/jats:sub>. Inhibition of other K<jats:sup>+<\/jats:sup> currents such as <jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub> is likely to be important at higher concentrations.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1998) <jats:bold>125<\/jats:bold>, 1138\u20131143; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702173\">10.1038\/sj.bjp.0702173<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702173","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:52:52Z","timestamp":1106941972000},"page":"1138-1143","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Inhibition of the rapid component of the delayed\u2010rectifier K<sup>+<\/sup> current by therapeutic concentrations of the antispasmodic agent terodiline"],"prefix":"10.1111","volume":"125","author":[{"given":"Stephen E","family":"Jones","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshitsugu","family":"Ogura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lesya M","family":"Shuba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terence F","family":"McDonald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.69.2.519"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.91.8.2220"},{"key":"e_1_2_6_4_1","first-page":"809","article-title":"Voltage\u2010 and time\u2010dependent block of the delayed K+ current in cardiac myocytes by dofetilide","volume":"262","author":"Carmeliet E.","year":"1992","journal-title":"J. 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