hERG Blockade by Iboga Alkaloids.
Cardiovascular toxicology January 1, 2016 Kenneth Alper, Rong Bai, Nian Liu et al. 35 citations
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.