{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:53:59Z","timestamp":1792065239585,"version":"4.4.0"},"reference-count":30,"publisher":"Japanese Pharmacological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Pharmacol Sci"],"published-print":{"date-parts":[[2005]]},"DOI":"10.1254\/jphs.qt-c8","type":"journal-article","created":{"date-parts":[[2006,2,6]],"date-time":"2006-02-06T05:56:34Z","timestamp":1139205394000},"page":"449-457","source":"Crossref","is-referenced-by-count":19,"title":["QT PRODACT: Evaluation of the Potential of Compounds to Cause QT Interval Prolongation by Action Potential Assays Using Guinea-Pig Papillary Muscles"],"prefix":"10.1254","volume":"99","author":[{"given":"Yoshihide","family":"Kii","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiji","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuyasu","family":"Tabo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Shimosato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Fukuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuji","family":"Itoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideto","family":"Amano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamoru","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Morimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuhiro","family":"Kanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshimasa","family":"Ishitsuka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanobu","family":"Yamazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichi","family":"Kiuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Taniguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigekazu","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Tsurubuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun-ichi","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-ichi","family":"Kitani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiaki","family":"Shimada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaharu","family":"Komeno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chieko","family":"Kasai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyasu","family":"Hombo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiji","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"332","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1 Redfern WS, Carlsson L, Davis AS, Lynch WG, MacKenzie I, Palethorpe S, et al. Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development. Cardiovasc Res. 2003;58:32–45. (The full, electronic version of this article is available on; http:\/\/www.elsevier.com\/homepage\/sab\/cardio\/doc\/Redfern_full.pdf).","DOI":"10.1016\/S0008-6363(02)00846-5"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2 Curtis LH, Ostbye T, Sendersky V, Hutchison S, Allen LaPointe NM, Al-Khatib SM, et al. Prescription of QT-prolonging drugs in a cohort of about 5 million outpatients. Am J Med. 2003;114:135–141.","DOI":"10.1016\/S0002-9343(02)01455-9"},{"key":"3","unstructured":"3 ICH Harmonised Tripartite Guideline, The Non-clinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals S7B. Recommended for adoption at step 4 of the ICH process on 12 May 2005 by the ICH Steering Committee. ICH; http:\/\/www.ich.org\/."},{"key":"4","doi-asserted-by":"crossref","unstructured":"4 Hayashi S, Kii Y, Tabo M, Fukuda H, Itoh T, Shimosato T, et al. QT PRODACT: A multi-site study of in vitro action potential assays on 21 compounds in isolated guinea-pig papillary muscles. J Pharmacol Sci. 2005;99:423–437.","DOI":"10.1254\/jphs.QT-A1"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5 Hondeghem LM, Carlsson L, Duker G. Instability and triangulation of the action potential predict serious proarrhythmia, but action potential duration prolongation is antiarrhythmic. Circulation. 2001;103:2004–2013.","DOI":"10.1161\/01.CIR.103.15.2004"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6 Hondeghem LM, Lu HR, van Rossem K, De Clerck F. Detection of proarrhythmia in the female rabbit heart: blinded validation. Cardiovasc Electrophysiol. 2003;14:287–294.","DOI":"10.1046\/j.1540-8167.2003.02466.x"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7 Martin RL, McDermott JS, Salmen HJ, Palmatier J, Cox BF, Gintant GA. The utility of hERG and repolarization assays in evaluating delayed cardiac repolarization: influence of multi-channel block. J Cardiovasc Pharmacol. 2004;43:369–379.","DOI":"10.1097\/00005344-200403000-00007"},{"key":"8","unstructured":"8 Snyders DJ, Chaudhary A. High affinity open channel block by dofetilide of HERG expressed in a human cell line. Mol Pharmacol. 1996;49:949–955."},{"key":"9","doi-asserted-by":"crossref","unstructured":"9 Lu HR, Vlaminckx E, Van Ammel K, De Clerck F. Drug-induced long QT in isolated rabbit Purkinje fibers: importance of action potential duration, triangulation and early afterdepolarizations. Eur J Pharmacol. 2002;452:183–192.","DOI":"10.1016\/S0014-2999(02)02246-X"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10 Matsuoka S, Sarai N, Kuratomi S, Ono K, Noma A. Role of individual ionic current systems in ventricular cells hypothesized by a model study. Jpn J Physiol. 2003;53:105–123.","DOI":"10.2170\/jjphysiol.53.105"},{"key":"11","unstructured":"11 Yatani A, Brown AM, Schwartz A. Bepridil block of cardiac calcium and sodium channels. J Pharmacol Exp Ther. 1986;237:9–17."},{"key":"12","doi-asserted-by":"crossref","unstructured":"12 Chiang CE, Wang TM, Luk HN. Inhibition of L-type Ca2+<\/sup> current in guinea pig ventricular myocytes by cisapride. J Biomed Sci. 2004;11:303–314.","DOI":"10.1007\/BF02254434"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13 Hiraoka M, Kuga K, Kawano S, Sunami A, Fan Z. New observations on the mechanisms of antiarrhythmic actions of disopyramide on cardiac membranes. Am J Cardiol. 1989;64:15J–19J.","DOI":"10.1016\/0002-9149(89)91191-0"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14 Scamps F, Undrovinas A, Vassort G. Inhibition of ICa<\/sub> in single frog cardiac cells by quinidine, flecainide, ethmozin, and ethacizin. Am J Physiol. 1989;256:C549–C559.","DOI":"10.1152\/ajpcell.1989.256.3.C549"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15 Buckley NA, Sanders P. Cardiovascular adverse effects of antipsychotic drugs. Drug Saf. 2000;23:215–228.","DOI":"10.2165\/00002018-200023030-00004"},{"key":"16","unstructured":"16 Enyeart JJ, Dirksen RT, Sharma VK, Williford DJ, Sheu SS. Antipsychotic pimozide is a potent Ca2+<\/sup> channel blocker in heart. Mol Pharmacol. 1990;37:752–757."},{"key":"17","doi-asserted-by":"crossref","unstructured":"17 Michel D, Wegener JW, Nowrath H. Effects of quinine and quinidine on the transient outward and on the L-type Ca2+<\/sup> current in rat ventricular cardiomyocytes. Pharmacology. 2002;65:187–192.","DOI":"10.1159\/000064342"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18 Ming Z, Nordin C. Terfenadine blocks time-dependent Ca2+<\/sup>, Na+<\/sup>, and K+<\/sup> channels in guinea pig ventricular myocytes. J Cardiovasc Pharmacol. 1995;26:761–769.","DOI":"10.1097\/00005344-199511000-00013"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19 Liu S, Melchert RB, Kennedy RH. Inhibition of L-type Ca2+<\/sup> channel current in rat ventricular myocytes by terfenadine. Circ Res. 1997;81:202–210.","DOI":"10.1161\/01.RES.81.2.202"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20 Wegener JW, Nawrath H. Extracellular site of action of phenylalkylamines on L-type calcium current in rat ventricular myocytes. Naunyn Schmiedebergs Arch Pharmacol. 1995;352:322–330.","DOI":"10.1007\/BF00168564"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21 Omata T, Kasai C, Hashimoto M, Hombo T, Yamamoto K. QT PRODACT: Comparison of non-clinical studies for drug-induced delay in ventricular repolarization and their role in safety evaluation in humans. J Pharmacol Sci. 2005;99:531–541.","DOI":"10.1254\/jphs.QT-C12"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22 Khalifa M, Drolet B, Daleau P, Lefez C, Gilbert M, Plante S, et al. Block of potassium currents in guinea pig ventricular myocytes and lengthening of cardiac repolarization in man by the histamine H1 receptor antagonist diphenhydramine. J Pharmacol Exp Ther. 1999;288:858–865.","DOI":"10.1016\/S0022-3565(24)38031-0"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23 Salata JJ, Jurkiewicz NK, Wallace AA, Stupienski RF III, Guinosso PJ Jr, Lynch JJ Jr. Cardiac electrophysiological actions of the histamine H1<\/sub>-receptor antagonists astemizole and terfenadine compared with chlorpheniramine and pyrilamine. Circ Res. 1995;76:110–119.","DOI":"10.1161\/01.RES.76.1.110"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24 Drolet B, Khalifa M, Daleau P, Hamelin BA, Turgeon J. Block of the rapid component of the delayed rectifier potassium current by the prokinetic agent cisapride underlies drug-related lengthening of the QT interval. Circulation. 1998;97:204–210.","DOI":"10.1161\/01.CIR.97.2.204"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25 Sanguinetti MC, Jurkiewicz NK. Two components of cardiac delayed rectifier K+<\/sup> current. Differential sensitivity to block by class III antiarrhythmic agents. J Gen Physiol. 1990;96:195–215.","DOI":"10.1085\/jgp.96.1.195"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26 Wang DW, Kiyosue T, Sato T, Arita M. Comparison of the effects of class I anti-arrhythmic drugs, cibenzoline, mexiletine and flecainide, on the delayed rectifier K+<\/sup> current of guinea-pig ventricular myocytes. J Mol Cell Cardiol. 1996;28:893–903.","DOI":"10.1006\/jmcc.1996.0084"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27 Kang J, Wang L, Chen XL, Triggle DJ, Rampe D. Interactions of a series of fluoroquinolone antibacterial drugs with the human cardiac K+<\/sup> channel HERG. Mol Pharmacol. 2001;59:122–126.","DOI":"10.1124\/mol.59.1.122"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28 Kang J, Wang L, Cai F, Rampe D. High affinity blockade of the HERG cardiac K+<\/sup> channel by the neuroleptic pimozide. Eur J Pharmacol. 2000;392:137–140.","DOI":"10.1016\/S0014-2999(00)00123-0"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29 Kang J, Chen XL, Wang L, Rampe D. Interactions of the antimalarial drug mefloquine with the human cardiac potassium channels KvLQT1\/minK and HERG. J Pharmacol Exp Ther. 2001;299:290–296.","DOI":"10.1016\/S0022-3565(24)29329-0"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30 Dupuis DS, Klaerke DA, Olesen SP. Effect of β-adrenoceptor blockers on human ether-a-go-go-related gene (HERG) potassium channels. Basic Clin Pharmacol Toxicol. 2005;96:123–130.","DOI":"10.1111\/j.1742-7843.2005.pto960206.x"}],"container-title":["Journal of Pharmacological Sciences"],"original-title":[],"language":"en","deposited":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T16:23:41Z","timestamp":1736267021000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/jphs\/99\/5\/99_5_449\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005]]},"references-count":30,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2005]]}},"URL":"https:\/\/doi.org\/10.1254\/jphs.qt-c8","relation":{},"ISSN":["1347-8613","1347-8648"],"issn-type":[{"value":"1347-8613","type":"print"},{"value":"1347-8648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005]]}}}