{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:22:18Z","timestamp":1792059738305,"version":"4.4.0"},"reference-count":82,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2015,1,29]],"date-time":"2015-01-29T00:00:00Z","timestamp":1422489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The plant indole alkaloid ibogaine has shown promising anti-addictive properties in animal studies. Ibogaine is also anti-addictive in humans as the drug alleviates drug craving and impedes relapse of drug use. Although not licensed as therapeutic drug and despite safety concerns, ibogaine is currently used as an anti-addiction medication in alternative medicine in dozens of clinics worldwide. In recent years, alarming reports of life-threatening complications and sudden death cases, temporally associated with the administration of ibogaine, have been accumulating. These adverse reactions were hypothesised to be associated with ibogaine\u2019s propensity to induce cardiac arrhythmias. The aim of this review is to recapitulate the current knowledge about ibogaine\u2019s effects on the heart and the cardiovascular system, and to assess the cardiac risks associated with the use of this drug in anti- addiction therapy. The actions of 18-methoxycoronaridine (18-MC), a less toxic ibogaine congener with anti-addictive properties, are also considered.<\/jats:p>","DOI":"10.3390\/molecules20022208","type":"journal-article","created":{"date-parts":[[2015,1,29]],"date-time":"2015-01-29T10:10:02Z","timestamp":1422526202000},"page":"2208-2228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":114,"title":["The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation"],"prefix":"10.3390","volume":"20","author":[{"given":"Xaver","family":"Koenig","sequence":"first","affiliation":[{"name":"Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, Vienna 1090, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karlheinz","family":"Hilber","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, Vienna 1090, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1111\/j.1556-4029.2011.02008.x","article-title":"Fatalities Temporally Associated with the Ingestion of Ibogaine","volume":"57","author":"Alper","year":"2012","journal-title":"J. Forensic. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0099-9598(01)56005-8","article-title":"Ibogaine: A review","volume":"56","author":"Alper","year":"2001","journal-title":"Alkaloids Chem. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/j.1749-6632.1998.tb08237.x","article-title":"Mechanisms of antiaddictive actions of ibogaine","volume":"844","author":"Glick","year":"1998","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/j.1749-6632.2000.tb05211.x","article-title":"18-Methoxycoronaridine (18-MC) and ibogaine: Comparison of antiaddictive efficacy, toxicity, and mechanisms of action","volume":"914","author":"Glick","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1177\/0960327107087802","article-title":"Ibogaine, an anti-addictive drug: Pharmacology and time to go further in development. A narrative review","volume":"27","author":"Maciulaitis","year":"2008","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2174\/15672050113109990001","article-title":"Ibogaine in the treatment of substance dependence","volume":"6","author":"Brown","year":"2013","journal-title":"Curr. Drug Abuse Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1111\/j.1749-6632.2000.tb05210.x","article-title":"Noribogaine (12-hydroxyibogamine): A biologically active metabolite of the antiaddictive drug ibogaine","volume":"914","author":"Baumann","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/S0022-3565(24)29567-7","article-title":"In vivo neurobiological effects of ibogaine and its O-desmethyl metabolite, 12-hydroxyibogamine (noribogaine), in rats","volume":"297","author":"Baumann","year":"2001","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1111\/j.1749-6632.2000.tb05213.x","article-title":"Ibogaine: Complex pharmacokinetics, concerns for safety, and preliminary efficacy measures","volume":"914","author":"Mash","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_10","first-page":"92","article-title":"Analysis of the cardiovascular action of ibogaine hydrochlorid","volume":"110","author":"Schneider","year":"1957","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1126\/science.308.5720.345","article-title":"Addiction research. Ibogaine therapy: A \u201cvast, uncontrolled experiment\u201d","volume":"308","author":"Vastag","year":"2005","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e77262","DOI":"10.1371\/journal.pone.0077262","article-title":"Effect of Iboga alkaloids on micro-opioid receptor-coupled G protein activation","volume":"8","author":"Antonio","year":"2013","journal-title":"PLoS One"},{"key":"ref_13","unstructured":"National Institutes of Health. (2013) ND-Enabling Studies and GMP Scale-Up of 18-Methoxycoronaridine Hydrochloride (18 MC) Project Number: 1U01DA034986-01, Available online: http:\/\/projectreporter.nih.gov\/project_info_description.cfm?aid=8448461&icde=16047111&ddparam=&ddvalue=&ddsub=&cr=41&csb=default&cs=ASC."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/0006-8993(96)00056-X","article-title":"18-Methoxycoronaridine, a non-toxic iboga alkaloid congener: Effects on morphine and cocaine self-administration and on mesolimbic dopamine release in rats","volume":"719","author":"Glick","year":"1996","journal-title":"Brain Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0099-9598(01)56006-X","article-title":"Mechanisms of action of ibogaine: Relevance to putative therapeutic effects and development of a safer iboga alkaloid congener","volume":"56","author":"Glick","year":"2001","journal-title":"Alkaloids Chem. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ejphar.2011.08.001","article-title":"Brain regions mediating alpha3beta4 nicotinic antagonist effects of 18-MC on nicotine self-administration","volume":"669","author":"Glick","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.taap.2013.05.012","article-title":"Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: A study to assess the drug\u2019s cardiac ion channel profile","volume":"273","author":"Koenig","year":"2013","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/0006-8993(96)00739-1","article-title":"Ibogaine neurotoxicity: A re-evaluation","volume":"737","author":"Molinari","year":"1996","journal-title":"Brain Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/0306-4522(93)90500-F","article-title":"Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline","volume":"55","author":"Molliver","year":"1993","journal-title":"Neuroscience"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1093\/toxsci\/57.1.95","article-title":"A dose-response study of ibogaine-induced neuropathology in the rat cerebellum","volume":"57","author":"Xu","year":"2000","journal-title":"Toxicol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1056\/NEJMc0804248","article-title":"Long-QT syndrome induced by the antiaddiction drug ibogaine","volume":"360","author":"Hoelen","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/S0008-6363(02)00846-5","article-title":"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","volume":"58","author":"Redfern","year":"2003","journal-title":"Cardiovasc. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nature04710","article-title":"hERG potassium channels and cardiac arrhythmia","volume":"440","author":"Sanguinetti","year":"2006","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.jflm.2013.06.032","article-title":"Ibogaine related sudden death: A case report","volume":"20","author":"Papadodima","year":"2013","journal-title":"J. Forensic Leg. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1111\/1556-4029.12250","article-title":"Fatal case of a 27-year-old male after taking iboga in withdrawal treatment: GC-MS\/MS determination of ibogaine and ibogamine in iboga roots and postmortem biological material","volume":"58","author":"Mazoyer","year":"2013","journal-title":"J. Forensic Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1111\/j.1521-0391.2012.00330.x","article-title":"A case of death due to ibogaine use for heroin addiction: Case report","volume":"22","author":"Jalal","year":"2013","journal-title":"Am. J. Addict."},{"key":"ref_27","first-page":"422","article-title":"Life-threatening complications of ibogaine: Three case reports","volume":"70","author":"Paling","year":"2012","journal-title":"Neth. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3109\/15563650.2011.647031","article-title":"Ibogaine-associated ventricular tachyarrhythmias","volume":"50","author":"Pleskovic","year":"2012","journal-title":"Clin. Toxicol."},{"key":"ref_29","first-page":"654","article-title":"Pause-dependent ventricular tachycardia and torsades de pointes after ibogaine ingestion","volume":"50","author":"Shawn","year":"2012","journal-title":"Clin. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1093\/bja\/aet396","article-title":"Growing menace of ibogaine toxicity","volume":"111","author":"Asua","year":"2013","journal-title":"Br. J. Anaesth."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"642","DOI":"10.3109\/15563650.2014.927477","article-title":"Cardiac arrest after ibogaine ingestion","volume":"52","author":"Vlaanderen","year":"2014","journal-title":"Clin. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1080\/1057563029001\/4881","article-title":"Extraction studies of Tabernanthe iboga and Voacanga africana","volume":"16","author":"Jenks","year":"2002","journal-title":"Nat. Prod. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3099","DOI":"10.1021\/ja00965a039","article-title":"The total synthesis of Iboga alkaloids","volume":"88","author":"Coffen","year":"1966","journal-title":"J. Am. Chem. Soc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7155","DOI":"10.1016\/j.tet.2012.06.027","article-title":"Total synthesis of ibogaine, epiibogaine and their analogues","volume":"68","author":"Jana","year":"2012","journal-title":"Tetrahedron"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0099-9598(01)56012-5","article-title":"Ibogaine in the treatment of heroin withdrawal","volume":"56","author":"Mash","year":"2001","journal-title":"Alkaloids Chem. Biol."},{"key":"ref_36","first-page":"764","article-title":"Cytochrome P4502D6 catalyzes the O-demethylation of the psychoactive alkaloid ibogaine to 12-hydroxyibogamine","volume":"26","author":"Obach","year":"1998","journal-title":"Drug Metab. Dispos."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"689","DOI":"10.2165\/11318030-000000000-00000","article-title":"Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I","volume":"48","author":"Zhou","year":"2009","journal-title":"Clin. Pharmacokinet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"L119","DOI":"10.1016\/0024-3205(95)02322-4","article-title":"Tissue distribution of ibogaine after intraperitoneal and subcutaneous administration","volume":"58","author":"Hough","year":"1996","journal-title":"Life Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1111\/j.1749-6632.1998.tb08242.x","article-title":"Medication development of ibogaine as a pharmacotherapy for drug dependence","volume":"844","author":"Mash","year":"1998","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Glue, P., Lockhart, M., Lam, F., Hung, N., Hung, C.T., and Friedhoff, L. (2014). Ascending-dose study of noribogaine in healthy volunteers: Pharmacokinetics, pharmacodynamics, safety, and tolerability. J. Clin. Pharmacol.","DOI":"10.1002\/jcph.404"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jchromb.2006.05.035","article-title":"Liquid chromatography-electrospray mass spectrometry determination of ibogaine and noribogaine in human plasma and whole blood. Application to a poisoning involving Tabernanthe iboga root","volume":"843","author":"Kontrimaviciute","year":"2006","journal-title":"J. Chromatogr. B"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1124\/dmd.30.6.663","article-title":"Metabolism of 18-methoxycoronaridine, an ibogaine analog, to 18-hydroxycoronaridine by genetically variable CYP2C19","volume":"30","author":"Zhang","year":"2002","journal-title":"Drug Metab. Dispos."},{"key":"ref_43","first-page":"441","article-title":"Effects of tabernanthine on various cardiovascular parameters in the rat and dog (author's transl)","volume":"12","author":"Hajo","year":"1981","journal-title":"J. Pharmacol."},{"key":"ref_44","first-page":"60","article-title":"Peripheral cardiovascular effects of tabernanthine tartrate in anaesthetized rats","volume":"276","author":"Hamon","year":"1985","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"ref_45","first-page":"35","article-title":"Effects of tabernanthine on calcium and catecholamine stimulated contractions of isolated vascular and cardiac muscle","volume":"276","author":"Dupont","year":"1985","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/j.1749-6632.1998.tb08241.x","article-title":"Alteration of electroencephalogram and monoamine concentrations in rat brain following ibogaine treatment","volume":"844","author":"Binienda","year":"1998","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_47","unstructured":"Harris, L.S. (1998, January 12\u201317). Ibogaine: Clinical observations of safety after single dose administrations. Problems of Drug Dependence, Proceedings of the 60th Annual Scientific Meeting, The College on Problems of Drug Dependence Inc., Scottsdale, Arizona."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1152\/jn.2002.87.6.2867","article-title":"Sigma receptors inhibit high-voltage-activated calcium channels in rat sympathetic and parasympathetic neurons","volume":"87","author":"Zhang","year":"2002","journal-title":"J. Neurophysiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/j.1749-6632.2000.tb06677.x","article-title":"Development of novel medications for drug addiction. The legacy of an African shrub","volume":"909","author":"Glick","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.jep.2011.12.006","article-title":"Ibogaine and the inhibition of acetylcholinesterase","volume":"139","author":"Alper","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/BF02245936","article-title":"Receptor binding profile suggests multiple mechanisms of action are responsible for ibogaine\u2019s putative anti-addictive activity","volume":"118","author":"Sweetnam","year":"1995","journal-title":"Psychopharmacology (Berl)"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/0006-8993(92)90661-R","article-title":"Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies","volume":"571","author":"Deecher","year":"1992","journal-title":"Brain Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.ejphar.2005.11.035","article-title":"Pharmacological characterisation of sodium channels in sinoatrial node pacemaking in the rat heart","volume":"530","author":"Letienne","year":"2006","journal-title":"Eur. J. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/S0749-0704(05)70371-7","article-title":"Poisoning by sodium channel blocking agents","volume":"13","author":"Kolecki","year":"1997","journal-title":"Crit. Care Clin."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.yjmcc.2006.12.005","article-title":"The promiscuous nature of the cardiac sodium current","volume":"42","author":"Haufe","year":"2007","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1093\/cvr\/cvm118","article-title":"Tissue distribution and subcellular localization of the cardiac sodium channel during mouse heart development","volume":"78","author":"Dominguez","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.yjmcc.2013.05.006","article-title":"Distribution and function of sodium channel subtypes in human atrial myocardium","volume":"61","author":"Kaufmann","year":"2013","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1085\/jgp.201310996","article-title":"The G-protein-gated K+ channel, IKACh, is required for regulation of pacemaker activity and recovery of resting heart rate after sympathetic stimulation","volume":"142","author":"Mesirca","year":"2013","journal-title":"J. Gen. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/j.1369-1600.2012.00447.x","article-title":"Anti-addiction drug ibogaine inhibits hERG channels: a cardiac arrhythmia risk","volume":"19","author":"Koenig","year":"2014","journal-title":"Addict. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1124\/jpet.113.209643","article-title":"Mechanism of hERG channel block by the psychoactive indole alkaloid ibogaine","volume":"348","author":"Thurner","year":"2014","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1159\/000064342","article-title":"Effects of quinine and quinidine on the transient outward and on the L-type Ca2+ current in rat ventricular cardiomyocytes","volume":"65","author":"Michel","year":"2002","journal-title":"Pharmacology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1097\/00005344-199902000-00002","article-title":"Modulation of HERG potassium channels by extracellular magnesium and quinidine","volume":"33","author":"Po","year":"1999","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_63","unstructured":"Ruan, Y., Bai, R., Liu, N., Fowler, S.J., Priori, S.G., Wang, L., Lin, L., Yu, R.H., Ma, C.S., and Alper, K. (September, January 30). Herg blockade by iboga alkaloids. Proceedings of the European Society of Cardiology Congress 2014, Barcelona, Spain."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.vascn.2005.03.008","article-title":"HERG-Lite: A novel comprehensive high-throughput screen for drug-induced hERG risk","volume":"52","author":"Wible","year":"2005","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1161\/01.CIR.103.15.2004","article-title":"Instability and triangulation of the action potential predict serious proarrhythmia, but action potential duration prolongation is antiarrhythmic","volume":"103","author":"Hondeghem","year":"2001","journal-title":"Circulation"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.jacc.2005.08.067","article-title":"Prolonged QTc interval and risk of sudden cardiac death in a population of older adults","volume":"47","author":"Straus","year":"2006","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nrd1108","article-title":"The impact of drug-induced QT interval prolongation on drug discovery and development","volume":"2","author":"Fermini","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1046\/j.1472-8206.2002.00083.x","article-title":"Drug-induced prolongation of the QT interval: Regulatory dilemmas and implications for approval and labelling of a new chemical entity","volume":"16","author":"Shah","year":"2002","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S0008-6363(00)00302-3","article-title":"Pharmacogenetics and drug-induced arrhythmias","volume":"50","author":"Roden","year":"2001","journal-title":"Cardiovasc. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1161\/01.CIR.93.3.407","article-title":"Extracellular potassium modulation of drug block of IKr implications for torsade de pointes and reverse use-dependence","volume":"93","author":"Yang","year":"1996","journal-title":"Circulation"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1124\/pr.110.003723","article-title":"Drug-induced long QT syndrome","volume":"62","author":"Kannankeril","year":"2010","journal-title":"Pharmacol. Rev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1111\/j.1472-8206.2010.00835.x","article-title":"Mechanisms of hypokalemia-induced ventricular arrhythmogenicity","volume":"24","author":"Osadchii","year":"2010","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1172\/JCI39027","article-title":"Extracellular K+ concentration controls cell surface density of IKr in rabbit hearts and of the HERG channel in human cell lines","volume":"119","author":"Guo","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1161\/01.RES.80.6.782","article-title":"Rapid inactivation determines the rectification and [K+]o dependence of the rapid component of the delayed rectifier K+ current in cardiac cells","volume":"80","author":"Yang","year":"1997","journal-title":"Circ. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1002\/clc.4960220910","article-title":"Effects of acute alcohol infusion on duration and dispersion of QT interval in male patients with coronary artery disease and in healthy controls","volume":"22","author":"Rossinen","year":"1999","journal-title":"Clin. Cardiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1124\/mol.59.2.269","article-title":"Inhibition of human ether-a-go-go potassium channels by cocaine","volume":"59","year":"2001","journal-title":"Mol. Pharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1097\/FJC.0b013e3181f1d21b","article-title":"Increased cardiac risk in concomitant methadone and diazepam treatment: Pharmacodynamic interactions in cardiac ion channels","volume":"56","author":"Kuryshev","year":"2010","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_78","first-page":"229","article-title":"Methadone, QTc prolongation and torsades de pointes: Current concepts, management and a hidden twist in the tale?","volume":"4","author":"Mujtaba","year":"2013","journal-title":"J. Cardiovasc. Dis. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1136\/pgmj.2004.022988","article-title":"Methadone: Applied pharmacology and use as adjunctive treatment in chronic pain","volume":"80","author":"Brown","year":"2004","journal-title":"Postgrad. Med. J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1111\/j.1365-2125.2012.04256.x","article-title":"Inhibition of CYP2D6-mediated tramadol O-demethylation in methadone but not buprenorphine maintenance patients","volume":"74","author":"Coller","year":"2012","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"913","DOI":"10.2165\/00003088-200241120-00002","article-title":"Clinical significance of the cytochrome P450 2C19 genetic polymorphism","volume":"41","author":"Desta","year":"2002","journal-title":"Clin. Pharmacokinet."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1161\/CIRCULATIONAHA.109.192704","article-title":"Prevention of Torsade de Pointes in Hospital Settings: A scientific statement from the American Heart Association and the American College of Cardiology Foundation","volume":"121","author":"Drew","year":"2010","journal-title":"Circulation"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/20\/2\/2208\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:42:07Z","timestamp":1760215327000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/20\/2\/2208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1,29]]},"references-count":82,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2015,2]]}},"alternative-id":["molecules20022208"],"URL":"https:\/\/doi.org\/10.3390\/molecules20022208","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,1,29]]}}}