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.

Modulation of the heart's electrical properties by the anticonvulsant drug retigabine

“…Action potentials (APs) were recorded from guinea pig ventricular cardiomyocytes and from ventricular-like hiPSC-derived cardiomyocytes in the current-clamp mode of the whole cell patch clamp technique at room temperature (22 ± 1 °C) as in (Koenig et al, 2013) and (Rubi et al, 2016). APs were elicited at 1 Hz by rectangular current pulses of 4 ms duration at 125% threshold level.…”

“…APs were elicited at 1 Hz by rectangular current pulses of 4 ms duration at 125% threshold level. Human cardiomyocytes were classified as ventricular-like when their APs showed a distinct “shoulder” (plateau or flat repolarization phase) prior to a final steep phase of repolarization as in our previous work (Rubi et al, 2016). The composition of the experimental solutions is given in (Koenig et al, 2013).…”

Pharmacological Profile of the Bradycardic Agent Ivabradine on Human Cardiac Ion Channels

“…Currents were recorded after 20-30 minutes when series resistance had Hächl et al: Ivabradine Effects on Human Cardiac Ion Channels stabilised below 12 MOhm. Action potentials (APs) were recorded from ''ventricular-like'' hiPS-CM in the current-clamp mode of the whole cell patch clamp technique as in our previous study [27] using both an Axoclamp 200B as well as an Axoclamp 700B amplifier. APs were elicited at 0.5 Hz by rectangular current pulses of 4 ms duration at 125 % threshold level.…”

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“…62 However, there were reports of cardiotoxicity and neurotoxicity associated with Tabernanthe iboga. 63,64 Nevertheless, if its anti-addictive properties are potentially effective, future studies should consider to modify the chemical composition of ibogaine in order to reduce its toxicity and enhance its safety.…”