Toxicology and applied pharmacology
December 1, 2013
Xaver Koenig, Michael Kovar, Lena Rubi et al.
46 citations
Ibogaine, a plant alkaloid used to treat drug addiction despite not being licensed, inhibits hERG potassium channels at low micromolar concentrations, which could disturb heart rhythm. At higher concentrations, it also reduces sodium and calcium currents. Its congener 18-MC blocks these ion channels with less potency. Unexpectedly, ibogaine did not prolong action potentials in guinea pig cardiomyocytes at low concentrations, and higher concentrations shortened them, likely because calcium channel inhibition counteracts hERG blockade effects. However, computer modeling of human ventricular cells suggested ibogaine does prolong the action potential in humans. The authors conclude therapeutic concentrations may prolong the QT interval, potentially leading to cardiac arrhythmias.
Cardiovascular toxicology
April 1, 2017
Lena Rubi, Daniel Eckert, Stefan Boehm et al.
18 citations
The anti-addiction drug ibogaine and its main metabolite noribogaine slow action potential repolarization in human heart cells, providing the first experimental proof that ibogaine poses a risk of cardiac arrhythmias for humans. Using whole-cell patch clamp recordings on human ventricular-like cardiomyocytes derived from induced pluripotent stem cells, therapeutic concentrations of both substances significantly retarded repolarization. This explains the delayed incidence of cardiac adverse events observed several days after ibogaine intake. The findings suggest that ibogaine may prolong the QT interval in the electrocardiogram, leading to life-threatening arrhythmias and sudden death.
BMC Pharmacology and Toxicology
September 1, 2012
Xaver Koenig, Michael Kovar, Lena Rubi et al.
Ibogaine, a plant alkaloid used in alternative medicine for addiction despite not being a licensed therapeutic, can disturb heart rhythm. At therapeutic concentrations it inhibits hERG potassium channels, which can cause life-threatening arrhythmias. This study examined ibogaine and its analog 18-methoxycoronaridine (18-MC) on cardiac ion channels using patch clamp techniques and computer simulations. Ibogaine reduced hERG currents at low micromolar concentrations (IC50, 4 µM) and, at higher concentrations, also inhibited sodium channels. 18-MC was less potent. In guinea-pig cardiomyocytes, ibogaine did not prolong the action potential at low concentrations; higher concentrations shortened it. Computer modeling suggested calcium channel blockade counteracts hERG inhibition's prolonging effect. Ibogaine is potentially proarrhythmic but may also have antiarrhythmic properties.