{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T03:08:01Z","timestamp":1771729681673,"version":"3.50.1"},"reference-count":72,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T00:00:00Z","timestamp":1697500800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pacing Clinical Electrophis"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mexiletine, a class Ib antiarrhythmic drug, exhibits its major antiarrhythmic effect via inhibition of the fast and late Na<jats:sup>+<\/jats:sup> currents in myocardial tissues that are dependent on the opening of Na<jats:sup>+<\/jats:sup> channels for their excitation. Through a comprehensive examination of mexiletine's therapeutic benefits and potential risks, we aim to provide valuable insights that reinforce its role as a vital therapeutic option for patients with ventricular arrhythmias, long QT syndrome, and other heart rhythm disorders. This review will highlight the current understandings of the antiarrhythmic effects and rationales for recent off\u2010label use and address the mortality and proarrhythmic effects of mexiletine utilizing published basic and clinical studies over the past five decades.<\/jats:p>","DOI":"10.1111\/pace.14846","type":"journal-article","created":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T11:00:33Z","timestamp":1697540433000},"page":"1348-1356","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Mexiletine: Antiarrhythmic mechanisms, emerging clinical applications and mortality"],"prefix":"10.1111","volume":"46","author":[{"given":"Farah","family":"Olleik","sequence":"first","affiliation":[{"name":"Lankenau Medical Center and Lankenau Institute for Medical Research  Wynnewood Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed Hussein","family":"Kamareddine","sequence":"additional","affiliation":[{"name":"Lankenau Medical Center and Lankenau Institute for Medical Research  Wynnewood Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenna","family":"Spears","sequence":"additional","affiliation":[{"name":"Lankenau Medical Center and Lankenau Institute for Medical Research  Wynnewood Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Tse","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Ion\u2010Molecular Function of Cardiovascular Disease Tianjin Institute of Cardiology Second Hospital of Tianjin Medical University  Tianjin PR China"},{"name":"Kent and Medway Medical School  Canterbury Kent UK"},{"name":"School of Nursing and Health Studies Hong Kong Metropolitan University  Hong Kong PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Ion\u2010Molecular Function of Cardiovascular Disease Tianjin Institute of Cardiology Second Hospital of Tianjin Medical University  Tianjin PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3118-5680","authenticated-orcid":false,"given":"Gan\u2010Xin","family":"Yan","sequence":"additional","affiliation":[{"name":"Lankenau Medical Center and Lankenau Institute for Medical Research  Wynnewood Pennsylvania USA"},{"name":"Fuwai Huazhong Hospital Chinese Academy of Medical Sciences  Zhengzhou PR China"},{"name":"Sidney Kimmel Medical College at Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,10,17]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(73)92270\u20108"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.1982.tb04969.x"},{"key":"e_1_2_13_4_1","first-page":"505","article-title":"The effect of metoclopramide and atropine on the absorption of orally administered mexiletine","volume":"9","author":"Wing LM","year":"1980","journal-title":"Br J Clin Pharmacol"},{"key":"e_1_2_13_5_1","first-page":"115","article-title":"Electrophysiological properties of mexiletine assessed with respect to plasma concentrations","volume":"11","author":"Joseph SP","year":"1980","journal-title":"Eur J Cardiol"},{"key":"e_1_2_13_6_1","first-page":"55","article-title":"Pharmacokinetics of mexiletine in renal insufficiency","author":"Baudinet G","year":"1980","journal-title":"Acta Cardiol Suppl"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.1982.tb02003.x"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.1978.tb00833.x"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00547565"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/00912700222011265"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1991.140"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.205"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00614201"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.29.2267"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0735\u20101097(99)00488\u2010x"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2010.12.026"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2015.02.013"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacep.2022.10.031"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2008.02.009"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05688\u201011"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2133"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540\u20108167.1999.tb00287.x"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehn585"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.122.011453"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112701"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27791"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/pace.12109"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.113.000092"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2017.09.028"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13311"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476\u20105381.2010.00646.x"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0172683"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198908103210629"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv316"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.10.054"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euac087"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2013.10.033"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.92.12.3381"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.12.033"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2023.08.023"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.118.007280"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1536\/ihj.18\u2010724"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/jce.15517"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrcr.2022.08.003"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacep.2015.05.008"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2017.08.014"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2013.05.063"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2023.01.035"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.005482"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163619"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/eux221"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.94.6.1317a"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2007.10.029"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.12993"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/4078895"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(20)31108-6"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000139333.83620.5D"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.297.16.1775"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0735\u20101097(84)80133\u20103"},{"key":"e_1_2_13_60_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCINTERVENTIONS.118.007081"},{"key":"e_1_2_13_61_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.118.010004"},{"key":"e_1_2_13_62_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12872\u2010022\u201002628\u20103"},{"key":"e_1_2_13_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00380\u2010022\u201002145\u20105"},{"key":"e_1_2_13_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(80)92395\u20108"},{"key":"e_1_2_13_65_1","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.48.3.285"},{"key":"e_1_2_13_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00543481"},{"key":"e_1_2_13_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002\u20109149(90)91104\u2010e"},{"key":"e_1_2_13_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552\u20104604.1995.tb04091.x"},{"key":"e_1_2_13_69_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000426"},{"key":"e_1_2_13_70_1","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euac101"},{"key":"e_1_2_13_71_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344\u2010197901000\u201000005"},{"key":"e_1_2_13_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002\u20109149(82)90524\u20100"},{"key":"e_1_2_13_73_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.eurheartj.a061725"}],"container-title":["Pacing and Clinical Electrophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pace.14846","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T14:02:28Z","timestamp":1726322548000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pace.14846"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,17]]},"references-count":72,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1111\/pace.14846"],"URL":"https:\/\/doi.org\/10.1111\/pace.14846","archive":["Portico"],"relation":{},"ISSN":["0147-8389","1540-8159"],"issn-type":[{"value":"0147-8389","type":"print"},{"value":"1540-8159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,17]]},"assertion":[{"value":"2023-07-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}