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Michael Kovar

Center for Physiology and Pharmacology, Department of Neurophysiology and - pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria.

4 papers in the library · 101 citations · publishing 2011-2014

Papers

Anti-addiction drug ibogaine inhibits hERG channels: a cardiac arrhythmia risk.

Addiction biology March 1, 2014 Xaver Koenig, Michael Kovar, Stefan Boehm et al. 50 citations

Therapeutic concentrations of ibogaine, an alkaloid from the African shrub Tabernanthe iboga used in alternative medicine for its anti-addictive properties, reduce currents through human ether-a-go-go-related gene potassium channels. This provides a mechanism by which ibogaine may generate life-threatening cardiac arrhythmias, consistent with anecdotal evidence that it can disturb heart rhythm.

Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: a study to assess the drug's cardiac ion channel profile.

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.

The anti-addictive drug ibogaine modulates voltage-gated ion channels and may trigger cardiac arrhythmias

BMC Pharmacology September 5, 2011 Michael Kovar, Xaver Koenig, Ágnes K. Mike et al. 5 citations

Ibogaine, an alkaloid from the African shrub Tabernanthe iboga, has psychoactive properties and is being studied as a potential treatment for opioid, stimulant, alcohol, and nicotine addiction. However, its complex interactions with many cellular targets raise significant safety concerns. Beyond neurotoxic effects, ibogaine may harm the heart: several sudden deaths after use have been reported, possibly due to cardiac arrhythmias. In one case, a woman experienced a severely prolonged QT interval and ventricular tachyarrhythmias after taking ibogaine.

The anti-addiction drug ibogaine inhibits cardiac ion channels: a study to assess the drug’s proarrhythmic potential

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.