{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T07:01:03Z","timestamp":1768114863294,"version":"3.49.0"},"reference-count":21,"publisher":"Pharmaceutical Society of Japan","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biological &amp; Pharmaceutical Bulletin","Biol. Pharm. Bull."],"published-print":{"date-parts":[[2021,11,1]]},"DOI":"10.1248\/bpb.b21-00605","type":"journal-article","created":{"date-parts":[[2021,10,31]],"date-time":"2021-10-31T22:09:21Z","timestamp":1635718161000},"page":"1796-1799","source":"Crossref","is-referenced-by-count":2,"title":["Torsadogenic Potential of HCN Channel Blocker Ivabradine Assessed in the Rabbit Proarrhythmia Model"],"prefix":"10.1248","volume":"44","author":[{"given":"Akira","family":"Takahara","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megumi","family":"Aimoto","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinobu","family":"Nagasawa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"163","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1) Ide T, Ohtani K, Higo T, Tanaka M, Kawasaki Y, Tsutsui H. Ivabradine for the treatment of cardiovascular diseases. <i>Circ. J.<\/i>, <b>83<\/b>, 252\u2013260 (2019).","DOI":"10.1253\/circj.CJ-18-1184"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Koncz I, Sz\u00e9l T, Bitay M, Cerbai E, Jaeger K, F\u00fcl\u00f6p F, Jost N, Vir\u00e1g L, Orvos P, T\u00e1losi L, Krist\u00f3f A, Baczk\u00f3 I, Papp JG, Varr\u00f3 A. Electrophysiological effects of ivabradine in dog and human cardiac preparations: potential antiarrhythmic actions. <i>Eur. J. Pharmacol.<\/i>, <b>668<\/b>, 419\u2013426 (2011).","DOI":"10.1016\/j.ejphar.2011.07.025"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Mackiewicz U, Gerges JY, Chu S, Duda M, Dobrzynski H, Lewartowski B, M\u0105czewski M. Ivabradine protects against ventricular arrhythmias in acute myocardial infarction in the rat. <i>J. Cell. Physiol.<\/i>, <b>229<\/b>, 813\u2013823 (2014).","DOI":"10.1002\/jcp.24507"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) Vaillant F, Timour Q, Descotes J, Manati W, Belhani D, Bui-Xuan B, Tabib A, Bricca G, Chevalier P. Ivabradine induces an increase in ventricular fibrillation threshold during acute myocardial ischemia: an experimental study. <i>J. Cardiovasc. Pharmacol.<\/i>, <b>52<\/b>, 548\u2013554 (2008).","DOI":"10.1097\/FJC.0b013e3181913df4"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Jang JH, Kwon SW, Lee MJ, Ko KY, Park JH, Yoon GS, Choi SH, Beak YS, Park SD, Shin SH, Woo SI, Kim DH, Kwan J. Ivabradine-induced torsade de pointes in patients with heart failure reduced ejection fraction. <i>Int. Heart J.<\/i>, <b>61<\/b>, 1044\u20131048 (2020).","DOI":"10.1536\/ihj.20-073"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Cocco G, Jerie P. Torsades de pointes induced by the concomitant use of ivabradine and azithromycin: an unexpected dangerous interaction. <i>Cardiovasc. Toxicol.<\/i>, <b>15<\/b>, 104\u2013106 (2015).","DOI":"10.1007\/s12012-014-9274-y"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Kawakami S, Nagasawa Y, Hagiwara-Nagasawa M, Omura K, Aimoto M, Takahara A. Torsadogenic potential of a novel remyelinating drug clemastine for multiple sclerosis assessed in the rabbit proarrhythmia model. <i>J. Pharmacol. Sci.<\/i>, <b>144<\/b>, 123\u2013128 (2020).","DOI":"10.1016\/j.jphs.2020.08.003"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Hagiwara M, Shibuta S, Takada K, Kambayashi R, Nakajo M, Aimoto M, Nagasawa Y, Takahara A. The anaesthetized rabbit with acute atrioventricular block provides a new model for detecting drug-induced Torsade de Pointes. <i>Br. J. Pharmacol.<\/i>, <b>174<\/b>, 2591\u20132605 (2017).","DOI":"10.1111\/bph.13870"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Hagiwara M, Kambayashi R, Aimoto M, Nagasawa Y, Takahara A. <i>In vivo<\/i> analysis of torsadogenic potential of an antipsychotic drug paliperidone using the acute atrioventricular block rabbit as a proarrhythmia model. <i>J. Pharmacol. Sci.<\/i>, <b>132<\/b>, 48\u201354 (2016).","DOI":"10.1016\/j.jphs.2016.05.001"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Adgey AA. Warning arrhythmias in ischemic heart disease. <i>Int. J. Cardiol.<\/i>, <b>4<\/b>, 224\u2013228 (1983).","DOI":"10.1016\/0167-5273(83)90141-9"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Frommeyer G, Weller J, Ellermann C, Leitz P, Kochh\u00e4user S, Lange PS, Dechering DG, Eckardt L. Ivabradine aggravates the proarrhythmic risk in experimental models of long QT syndrome. <i>Cardiovasc. Toxicol.<\/i>, <b>19<\/b>, 129\u2013135 (2019).","DOI":"10.1007\/s12012-018-9482-y"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Manz M, Reuter M, Lauck G, Omran H, Jung W. A single intravenous dose of ivabradine, a novel I<sub>f<\/sub> inhibitor, lowers heart rate but does not depress left ventricular function in patients with left ventricular dysfunction. <i>Cardiology<\/i>, <b>100<\/b>, 149\u2013155 (2003).","DOI":"10.1159\/000073933"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) De Ferrari GM, Mazzuero A, Agnesina L, Bertoletti A, Lettino M, Campana C, Schwartz PJ, Tavazzi L. Favourable effects of heart rate reduction with intravenous administration of ivabradine in patients with advanced heart failure. <i>Eur. J. Heart Fail.<\/i>, <b>10<\/b>, 550\u2013555 (2008).","DOI":"10.1016\/j.ejheart.2008.04.005"},{"key":"14","unstructured":"14) Ono Pharmaceutical Co. Ltd. \u201cInterview Form: CORALAN<sup>\u00ae<\/sup> Tablets., 5th ed.\u201d: \u2039https:\/\/www.ononavi1717.jp\/system\/files\/2021-07\/CRL_IF.pdf\u203a, accessed 11 August, 2021."},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Riesen SC, Ni W, Carnes CA, Lindsey KJ, Phelps MA, Schober KE. Pharmacokinetics of oral ivabradine in healthy cats. <i>J. Vet. Pharmacol. Ther.<\/i>, <b>34<\/b>, 469\u2013475 (2011).","DOI":"10.1111\/j.1365-2885.2010.01253.x"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Chen XP, Zheng HT, Cai WW, Li MK, Zhang JW, Hu J. The effect of silibinin on the pharmacokinetics of ivabradine and N-desmethylivabradine in rats. <i>Pharmacology<\/i>, <b>96<\/b>, 107\u2013111 (2015).","DOI":"10.1159\/000435890"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) Varkevisser R, Wijers SC, van der Heyden MAG, Beekman JDM, Meine M, Vos MA. Beat-to-beat variability of repolarization as a new biomarker for proarrhythmia <i>in vivo.<\/i> <i>Heart Rhythm<\/i>, <b>9<\/b>, 1718\u20131726 (2012).","DOI":"10.1016\/j.hrthm.2012.05.016"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18) Bois P, Bescond J, Renaudon B, Lenfant J. Mode of action of bradycardic agent, S 16257, on ionic currents of rabbit sinoatrial node cells. <i>Br. J. Pharmacol.<\/i>, <b>118<\/b>, 1051\u20131057 (1996).","DOI":"10.1111\/j.1476-5381.1996.tb15505.x"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Melgari D, Brack KE, Zhang C, Zhang Y, El Harchi A, Mitcheson JS, Dempsey CE, Ng GA, Hancox JC. hERG potassium channel blockade by the HCN channel inhibitor bradycardic agent ivabradine. <i>J. Am. Heart Assoc.<\/i>, <b>4<\/b>, e001813 (2015).","DOI":"10.1161\/JAHA.115.001813"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20) Marger L, Mesirca P, Alig J, Torrente A, Dubel S, Engeland B, Kanani S, Fontanaud P, Striessnig J, Shin HS, Isbrandt D, Ehmke H, Nargeot J, Mangoni ME. Functional roles of Ca<sub>v<\/sub>1.3, Ca<sub>v<\/sub>3.1 and HCN channels in automaticity of mouse atrioventricular cells: insights into the atrioventricular pacemaker mechanism. <i>Channels <\/i>(Austin), <b>5<\/b>, 251\u2013261 (2011).","DOI":"10.4161\/chan.5.3.15266"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Hondeghem LM, Snyders DJ. Class III antiarrhythmic agents have a lot of potential but a long way to go. Reduced effectiveness and dangers of reverse use dependence. <i>Circulation<\/i>, <b>81<\/b>, 686\u2013690 (1990).","DOI":"10.1161\/01.CIR.81.2.686"}],"container-title":["Biological and Pharmaceutical Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/44\/11\/44_b21-00605\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,6]],"date-time":"2021-11-06T03:52:21Z","timestamp":1636170741000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/44\/11\/44_b21-00605\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,1]]},"references-count":21,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.1248\/bpb.b21-00605","relation":{},"ISSN":["0918-6158","1347-5215"],"issn-type":[{"value":"0918-6158","type":"print"},{"value":"1347-5215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,1]]},"article-number":"b21-00605"}}