{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T15:35:56Z","timestamp":1781796956248,"version":"3.54.5"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2251,"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":[[2002,12]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item>\n<jats:p>Levobupivacaine and ropivacaine are the pure S(\u2212) enantiomers of N\u2010butyl\u2010 and N\u2010propyl\u20102\u2032,6\u2032\u2010pipecoloxylidide, developed as less cardiotoxic alternatives to bupivacaine. In the present study, we have analysed the effects of levobupivacaine, ropivacaine and bupivacaine on <jats:italic>HERG<\/jats:italic> channels stably expressed in CHO cells.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>The three drugs blocked <jats:italic>HERG<\/jats:italic> channels in a concentration\u2010, time\u2010 and state\u2010dependent manner. Block measured at the end of 5 s pulses to \u221210 mV induced by 20 \u03bc<jats:sc>M<\/jats:sc> bupivacaine (52.7\u00b12.0%, <jats:italic>n<\/jats:italic>=15) and ropivacaine (55.5\u00b12.7%, <jats:italic>n<\/jats:italic>=13) was similar (<jats:italic>P<\/jats:italic>&gt;0.05) and both lower than that induced by levobupivacaine (67.5\u00b14.2%, <jats:italic>n<\/jats:italic>=11) (<jats:italic>P<\/jats:italic>&lt;0.05).<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Dextrobupivacaine (20 \u03bc<jats:sc>M<\/jats:sc>) was less potent (47.2\u00b15.2%, <jats:italic>n<\/jats:italic>=10) than levobupivacaine (<jats:italic>P<\/jats:italic>&lt;0.05), indicating stereoselective <jats:italic>HERG<\/jats:italic> channel block.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Block induced by the three local anaesthetics exhibited a steep voltage dependence in the range of channel activation. In all cases, block measured at the maximum peak current at a test potential of 0 mV after promoting recovery from inactivation (I\u2192O) was lower than that observed at the end of 5\u2010s pulses (I+O).<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Levobupivacaine, ropivacaine and bupivacaine accelerated <jats:italic>HERG<\/jats:italic> inactivation kinetics, slowed the recovery from inactivation and shifted the inactivation curve towards more negative membrane potentials. The three local anaesthetics induced a rapid time\u2010dependent decline after using a protocol that quickly activates <jats:italic>HERG<\/jats:italic> channels.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>All these results suggest that: (1) these drugs bind to the open and the inactivated states of <jats:italic>HERG<\/jats:italic> channels, (2) they stabilize <jats:italic>HERG<\/jats:italic> channels in the inactivated state, and (3) block induced by bupivacaine enantiomers is stereoselective.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2002) <jats:bold>137<\/jats:bold>, 1269\u20131279. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0704978\">10.1038\/sj.bjp.0704978<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0704978","type":"journal-article","created":{"date-parts":[[2002,12,4]],"date-time":"2002-12-04T18:22:03Z","timestamp":1039026123000},"page":"1269-1279","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Effects of levobupivacaine, ropivacaine and bupivacaine on <i>HERG<\/i> channels: stereoselective bupivacaine block"],"prefix":"10.1111","volume":"137","author":[{"given":"Teresa","family":"Gonz\u00e1lez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Arias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Caballero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Delp\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Tamargo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Valenzuela","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":"10.1111\/j.1600-0773.1972.tb00683.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-6576.1988.tb02788.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.58.4.413"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-198504000-00006"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200059030-00013"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1925602"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.81.6.1053"},{"key":"e_1_2_7_9_1","first-page":"581a","article-title":"Comparative effects of bupivacaine, levobupivacaine, and ropivacaine on HERG channels stably expressed in CHO cells","volume":"82","author":"GONZ\u00c1LEZ T.","year":"2002","journal-title":"Biophys. 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