title: Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
abstract: Ibogaine is a plant alkaloid used as anti-addiction drug in dozens of alternative medicine clinics worldwide. Recently, alarming reports of life-threatening cardiac arrhythmias and cases of sudden death associated with the ingestion of ibogaine have accumulated. Using whole-cell patch clamp recordings, we assessed the effects of ibogaine and its main metabolite noribogaine on action potentials in human ventricular-like cardiomyocytes derived from induced pluripotent stem cells. Therapeutic concentrations of ibogaine and its long-lived active metabolite noribogaine significantly retarded action potential repolarization in human cardiomyocytes. These findings represent the first experimental proof that ibogaine application entails a cardiac arrhythmia risk for humans. In addition, they explain the clinically observed delayed incidence of cardiac adverse events several days after ibogaine intake. We conclude that therapeutic concentrations of ibogaine retard action potential repolarization in the human heart. This may give rise to a prolongation of the QT interval in the electrocardiogram and cardiac arrhythmias.
authors.affiliation: Department of Neurophysiology and - Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, 1090, Vienna, Austria.
authors.forename: Lena
authors.initials: L
authors.lastname: Rubi
authors.affiliation: Department of Neurophysiology and - Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, 1090, Vienna, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Eckert
authors.affiliation: Department of Neurophysiology and - Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, 1090, Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Boehm
authors.affiliation: Department of Neurophysiology and - Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, 1090, Vienna, Austria. karlheinz.hilber@meduniwien.ac.at.
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Hilber
authors.affiliation: Department of Neurophysiology and - Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, 1090, Vienna, Austria.
authors.forename: Xaver
authors.initials: X
authors.lastname: Koenig
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D002454:Cell Differentiation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007050:Ibogaine / Q000031:analogs & derivatives / Q000633:toxicity*; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000633:toxicity*; D018408:Patch-Clamp Techniques; D018570:Risk Assessment; D019966:Substance-Related Disorders / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D018377:Neurotransmitter Agents; D007050:Ibogaine; C094385:noribogaine
keywords: Action potential repolarization; Anti-addiction drug ibogaine; Cardiac arrhythmias; Drug-induced QT interval prolongation; Human cardiomyocytes; Noribogaine