{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:42:51Z","timestamp":1790188971108,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2069,"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":[[2003,6]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Acquired long QT syndrome (aLQTS) is caused by prolongation of the cardiac action potential because of blockade of cardiac ion channels and delayed repolarization of the heart. Patients with aLQTS carry an increased risk for <jats:italic>torsade de pointes<\/jats:italic> arrhythmias and sudden cardiac death. Several antipsychotic drugs may cause aLQTS. Recently, cases of QTc prolongation and <jats:italic>torsade de pointes<\/jats:italic> associated with chlorpromazine treatment have been reported. Blockade of human ether\u2010a\u2010go\u2010go\u2010related gene (HERG) potassium channels, which plays a central role in arrhythmogenesis, has previously been reported to occur with chlorpromazine, but information on the mechanism of block is currently not available. We investigated the effects of chlorpromazine on cloned HERG potassium channels to determine the biophysical mechanism of block.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>HERG channels were heterologously expressed in <jats:italic>Xenopus laevis<\/jats:italic> oocytes, and ion currents were measured using the two\u2010microelectrode voltage\u2010clamp technique.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Chlorpromazine blocked HERG potassium channels with an IC<jats:sub>50<\/jats:sub> value of 21.6 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc> and a Hill coefficient of 1.11.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Analysis of the voltage dependence of block revealed a reduction of inhibition at positive membrane potentials.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Inhibition of HERG channels by chlorpromazine displayed reverse frequency dependence, that is, the amount of block was lower at higher stimulation rates. No marked changes in electrophysiological parameters such as voltage dependence of activation or inactivation, or changes of the inactivation time constant were observed.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In conclusion, HERG channels were blocked in the closed and activated states, and unblocking occurred very slowly.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2003) <jats:bold>139<\/jats:bold>, 567\u2013574. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705283\">10.1038\/sj.bjp.0705283<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705283","type":"journal-article","created":{"date-parts":[[2003,6,4]],"date-time":"2003-06-04T23:44:34Z","timestamp":1054770274000},"page":"567-574","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["The antipsychotic drug chlorpromazine inhibits HERG potassium channels"],"prefix":"10.1111","volume":"139","author":[{"given":"Dierk","family":"Thomas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kezhong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Kath\u00f6fer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo A","family":"Katus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Schoels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann","family":"Kiehn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph A","family":"Karle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/106002808802201007"},{"key":"e_1_2_7_3_1","first-page":"1261","article-title":"Thioridazine lengthens repolarization of cardiac ventricular myocytes by blocking the delayed rectifier potassium current","volume":"288","author":"DROLET B.","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.82.3.386"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.279.4.H1748"},{"key":"e_1_2_7_6_1","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1176\/appi.ajp.158.11.1774","article-title":"Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death","volume":"158","author":"GLASSMANN A.H.","year":"2001","journal-title":"Am. J. Psychiatry."},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200262110-00006"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.21.9.871.34565"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.59.1.122"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(00)00265-0"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.10.2572"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00005344"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1520-765X(01)90003-3"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(99)00181-1"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.115.3.229"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001573-200001000-00009"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199447010-00004"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2736(96)00205-2"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02035-3"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90340-2"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/379833a0"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0700989"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(96)00355-9"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702800"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.300.2.543"},{"key":"e_1_2_7_26_1","first-page":"753","article-title":"High\u2010affinity blockade of HERG human cardiac potassium channels by the novel antiarrhythmic drug BRL\u201032872","volume":"297","author":"THOMAS D.","year":"2001","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.39.27457"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)73083-X"},{"key":"e_1_2_7_29_1","first-page":"417","article-title":"Plasma concentrations of antipsychotic drugs in psychiatric inpatients","volume":"51","author":"TOKUNAGA H.","year":"1997","journal-title":"Nippon Hoigaku Zasshi"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)02107-8"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.8.3438"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704859"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0705283","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0705283","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0705283","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T22:28:13Z","timestamp":1697236093000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0705283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,6]]},"references-count":31,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2003,6]]}},"alternative-id":["10.1038\/sj.bjp.0705283"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0705283","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,6]]},"assertion":[{"value":"2009-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}