{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T01:31:03Z","timestamp":1777858263383,"version":"3.51.4"},"reference-count":25,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2007,9,1]],"date-time":"2007-09-01T00:00:00Z","timestamp":1188604800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2007,9]]},"abstract":"<jats:p>Prolongation of the QT interval has been observed during treatment with olanzapine, a thienobenzodiazepine antipsychotic agent. Our objectives were 1) to characterize the effects of olanzapine on cardiac repolarization and 2) to evaluate effects of olanzapine on the major time-dependent outward potassium current involved in cardiac repolarization, namely IKr (IKr: rapid component of the delayed rectifier potassium current).<\/jats:p>\n                  <jats:p>\n                    Isolated, buffer-perfused guinea pig hearts ( n = 40) were stimulated at different pacing cycle lengths (150\u2014250 msec) and exposed to olanzapine at concentrations ranging from 1 to 100 \u00b5M. Olanzapine increased monophasic action potential duration measured at 90% repolarization (MAPD90) in a concentration-dependent manner by 6.7 \u00b1 0.7 msec at 3 \u00b5M but by 26.0 \u00b1 4.3 msec at 100 \u00b5M (250 msec cycle length). Increase in MAPD\n                    <jats:sub>90<\/jats:sub>\n                    was also reverse frequency dependent; 30 \u00b5M olanzapine increased MAPD90 by 28.0 \u00b1 6.2 msec at a pacing cycle length of 250 msec but by only 18.9 \u00b1 2.2 msec at a pacing cycle length of 150 msec. Experiments in HERG-transfected (HERG: human ether-a-gogo-related gene) HEK293 cells ( n = 36) demonstrated concentration-dependent block of the rapid component (IKr) of the delayed rectifier potassium current: tail current was decreased 50% at olanzapine 3.8 \u00b5M.\n                  <\/jats:p>\n                  <jats:p>Olanzapine possesses direct cardiac electrophysiological effects similar to those of class III anti-arrhythmic drugs. These effects were observed at concentrations that can be measured in patients under conditions of impaired drug elimination such as renal or hepatic insufficiency, during co-administration of other CYP1A2 substrates\/inhibitors or after drug overdose. These results offer a new potential explanation for QT prolonging effects observed during olanzapine treatment in patients.<\/jats:p>","DOI":"10.1177\/0269881106072669","type":"journal-article","created":{"date-parts":[[2006,11,8]],"date-time":"2006-11-08T20:14:40Z","timestamp":1163016880000},"page":"735-741","source":"Crossref","is-referenced-by-count":30,"title":["Olanzapine prolongs cardiac repolarization by blocking the rapid component of                 the delayed rectifier potassium current"],"prefix":"10.1177","volume":"21","author":[{"given":"Pierre","family":"Morissette","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Universit\u00e9 de Montr\u00e9al,                         Montr\u00e9al, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond","family":"Hreiche","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Universit\u00e9 de Montr\u00e9al,                         Montr\u00e9al, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"Mallet","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Universit\u00e9 de Montr\u00e9al,                         Montr\u00e9al, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dean","family":"Vo","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta,                         Edmonton, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward E.","family":"Knaus","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta,                         Edmonton, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques","family":"Turgeon","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Universit\u00e9 de Montr\u00e9al,                         Montr\u00e9al, Canada,"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2007,9,1]]},"reference":[{"key":"atypb1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1995.00430070125014"},{"key":"atypb2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.70.5.469"},{"key":"atypb3","doi-asserted-by":"crossref","first-page":"177","DOI":"10.2165\/00003088-199937030-00001","volume":"37","author":"Callaghan J.T.","year":"1999","journal-title":"Clin Pharmacokinet"},{"key":"atypb4","unstructured":"Chakrabarti J K.                 ,                      Hotten T.M.                 ,                      Tupper D.E.                  (1993) 2-Methyl-thieno-benzodiazepine. United States                 Patent 5,229,382, Issued July 20, 1993. 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