Ibogaine, a compound used to treat addiction, can cause dangerous heart rhythm problems by blocking hERG potassium channels. This study measured how strongly several iboga alkaloids block hERG channels in human cells. Ibogaine and its metabolite noribogaine blocked hERG channels with IC50 values around 2-4 µM, while 18-methoxycoronaridine (18-MC), a synthetic derivative, showed much weaker blockade (IC50 >50 µM). Although 18-MC bound to hERG channels with similar affinity as other compounds, it produced substantially less channel blockade. These findings suggest that 18-MC may have a safer cardiac profile than ibogaine, and that the structural differences among iboga alkaloids offer a useful model for studying hERG channel biology.
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.