{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:58:03Z","timestamp":1788245883357,"version":"build-2803163510"},"reference-count":30,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2011,2,11]],"date-time":"2011-02-11T00:00:00Z","timestamp":1297382400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cardiovasc Pharmacol Ther"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:p>\n                    Background: Tizanidine (Zanaflex) is a centrally acting imidazoline muscle relaxant that is structurally similar to clonidine (\u03b1\n                    <jats:sub>2<\/jats:sub>\n                    -adrenergic agonist) but not to other myorelaxants such as baclofen or benzodiazepines. Interestingly, cardiac arrhythmias and QT interval prolongation have been reported with tizanidine. Objective: To evaluate the effects of tizanidine on cardiac ventricular repolarization. Methods: (1) Whole-cell patch-clamp experiments: HERG- or KCNQ1+KCNE1-transfected cells were exposed to tizanidine 0.1-100 \u00b5mol\/L (n = 29 cells, total) to assess drug effect on the rapid (I\n                    <jats:sub>Kr<\/jats:sub>\n                    ) and slow (I\n                    <jats:sub>Ks<\/jats:sub>\n                    ) components of the delayed rectifier potassium current. (2) Langendorff retroperfusion experiments: isolated hearts from male Hartley guinea pigs (n = 6) were exposed to tizanidine 1 \u00b5mol\/L to assess drug-induced prolongation of monophasic action potential duration measured at 90% repolarization (MAPD\n                    <jats:sub>90<\/jats:sub>\n                    ). (3) In vivo wireless cardiac telemetry experiments: guinea pigs (n = 6) implanted with radio transmitters were injected a single intraperitoneal (ip) dose of tizanidine 0.25 mg\/kg and 24 hours electrocardiography (ECG) recordings were made. Results: (1) Patch-clamp experiments revealed an estimated IC\n                    <jats:sub>50<\/jats:sub>\n                    for tizanidine on I\n                    <jats:sub>Kr<\/jats:sub>\n                    above 100 \u00b5mol\/L. Moreover, tizanidine 1 \u00b5mol\/L had hardly any effect on I\n                    <jats:sub>Ks<\/jats:sub>\n                    (5.23% \u00b1 4.54% inhibition, n = 5 cells). (2) While pacing the hearts at stimulation cycle lengths of 200 or 250 ms, tizanidine 1 \u00b5mol\/L prolonged MAPD\n                    <jats:sub>90<\/jats:sub>\n                    by 8.22 \u00b1 2.03 (6.7%) and 11.70 \u00b1 3.08 ms (8.5%), respectively (both P &lt; .05 vs baseline). (3) Tizanidine 0.25 mg\/kg ip caused a maximal 11.93 \u00b1 1.49 ms prolongation of corrected QT interval (QTc), 90 minutes after injection. Conclusion: Tizanidine prolongs the QT interval by blocking I\n                    <jats:sub>Kr<\/jats:sub>\n                    . Patients could be at risk of cardiac proarrhythmia during impaired drug elimination, such as in case of CYP1A2 inhibition during drug interactions.\n                  <\/jats:p>","DOI":"10.1177\/1074248410395020","type":"journal-article","created":{"date-parts":[[2011,2,12]],"date-time":"2011-02-12T00:19:09Z","timestamp":1297469949000},"page":"102-109","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":26,"title":["Tizanidine (Zanaflex)"],"prefix":"10.1177","volume":"17","author":[{"given":"Nisrin","family":"Kaddar","sequence":"first","affiliation":[{"name":"Centre de recherche de l\u2019Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec, Qu\u00e9bec, QC Canada"},{"name":"Facult\u00e9 de pharmacie, Universit\u00e9 Laval, Qu\u00e9bec, QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Vigneault","sequence":"additional","affiliation":[{"name":"Centre de recherche de l\u2019Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec, Qu\u00e9bec, QC Canada"},{"name":"Facult\u00e9 de pharmacie, Universit\u00e9 Laval, Qu\u00e9bec, QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Pilote","sequence":"additional","affiliation":[{"name":"Centre de recherche de l\u2019Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec, Qu\u00e9bec, QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dany","family":"Patoine","sequence":"additional","affiliation":[{"name":"Centre de recherche de l\u2019Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec, Qu\u00e9bec, QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantale","family":"Simard","sequence":"additional","affiliation":[{"name":"Centre de recherche de l\u2019Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec, Qu\u00e9bec, QC Canada"},{"name":"Facult\u00e9 de pharmacie, Universit\u00e9 Laval, Qu\u00e9bec, QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Drolet","sequence":"additional","affiliation":[{"name":"Centre de recherche de l\u2019Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec, Qu\u00e9bec, QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2011,2,11]]},"reference":[{"issue":"5","key":"bibr1-1074248410395020","first-page":"793","volume":"30","author":"Sayers AC","year":"1980","journal-title":"Arzneimittelforschung"},{"issue":"4","key":"bibr2-1074248410395020","first-page":"9","volume":"26","author":"Mathias CJ","year":"1989","journal-title":"J Rehabil Res Dev"},{"key":"bibr3-1074248410395020","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1983.tb10487.x"},{"key":"bibr4-1074248410395020","doi-asserted-by":"publisher","DOI":"10.1016\/0306-3623(86)90130-8"},{"key":"bibr5-1074248410395020","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201X.1996.444159000.x"},{"key":"bibr6-1074248410395020","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-6576.1995.tb04139.x"},{"key":"bibr7-1074248410395020","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2007.01660.x"},{"issue":"6","key":"bibr8-1074248410395020","first-page":"556","volume":"37","author":"Luciani A","year":"1995","journal-title":"Vet Hum Toxicol"},{"key":"bibr9-1074248410395020","doi-asserted-by":"publisher","DOI":"10.1185\/03007998809111122"},{"key":"bibr10-1074248410395020","doi-asserted-by":"publisher","DOI":"10.1185\/03007998809111121"},{"key":"bibr11-1074248410395020","doi-asserted-by":"publisher","DOI":"10.1111\/j.1774-9987.2005.00206.x"},{"key":"bibr12-1074248410395020","doi-asserted-by":"publisher","DOI":"10.1007\/s00063-005-1024-2"},{"key":"bibr13-1074248410395020","doi-asserted-by":"publisher","DOI":"10.2165\/11316090-000000000-00000"},{"issue":"1","key":"bibr14-1074248410395020","first-page":"53","volume":"107","author":"Del Rosario ME","year":"2010","journal-title":"Mo Med"},{"key":"bibr15-1074248410395020","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2008.00312.x"},{"key":"bibr16-1074248410395020","doi-asserted-by":"publisher","DOI":"10.1046\/j.1472-8206.2002.00081.x"},{"key":"bibr17-1074248410395020","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199753030-00007"},{"key":"bibr18-1074248410395020","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/30.5.331"},{"key":"bibr19-1074248410395020","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-006-0070-7"},{"key":"bibr20-1074248410395020","unstructured":"Tizanidine (Zanaflex\n                      tm\n                      ) Prescribing Information. 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