hERG Blockade by Iboga Alkaloids

  title={hERG Blockade by Iboga Alkaloids},
  author={Kenneth Alper and Rong Bai and Nian Liu and Steven J. Fowler and Xi-Ping Huang and Silvia Giuliana Priori and Yanfei Ruan},
  journal={Cardiovascular Toxicology},
AbstractThe iboga alkaloids are a class of naturally occurring and synthetic compounds, some of which modify drug self-administration and withdrawal in humans and preclinical models. Ibogaine, the prototypic iboga alkaloid that is utilized clinically to treat addictions, has been associated with QT prolongation, torsades de pointes and fatalities. hERG blockade as IKr was measured using the whole-cell patch clamp technique in HEK 293 cells. This yielded the following IC50 values: ibogaine… 

The iboga enigma: the chemistry and neuropharmacology of iboga alkaloids and related analogs.

This review will cover recent advances in both the biosynthesis and chemical synthesis of iboga alkaloids as well as their use as next-generation neurotherapeutics and historical context for the discoveries of the past decade is provided.

Biosynthesis of an Anti-Addiction Agent from the Iboga Plant

Discovery of these biosynthetic enzymes demonstrates how nature generates both enantiomeric series of this medically important alkaloid scaffold using closely related enzymes, including those that catalyze enantioselective formal Diels-Alder reactions.

hERG Channel Blocking Ipecac Alkaloids Identified by Combined In Silico - In Vitro Screening.

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DARK Classics in Chemical Neuroscience: Ibogaine.

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The adverse events of ibogaine in humans: an updated systematic review of the literature (2015–2020)

There is a high need of phase I clinical trials that can describe the safety of different dosages of ibogaine with standardized products and further research should perform clinical profiling of vulnerable populations, and design effective screening methods and clinical procedures.

Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

It is concluded that therapeutic concentrations of ibogaine retard action potential repolarization in the human heart, which may give rise to a prolongation of the QT interval in the electrocardiogram and cardiac arrhythmias.

Human Ether-à-go-go Related Gene (hERG) Channel Blocking Aporphine Alkaloids from Lotus Leaves and Their Quantitative Analysis in Dietary Weight Loss Supplements.

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In reply – on the toxicity of ibogaine

It is agreed that neurotoxicity is most likely not to occur at doses reported in therapeutic treatments, but questions their suggestion that some of the doses used in therapy could be considered ‘‘safe’’, like in Mash et al.



Effect of Iboga Alkaloids on µ-Opioid Receptor-Coupled G Protein Activation

Evidence regarding the activation of μ-opioid receptor (MOR)-related G proteins by iboga alkaloids is replicated and extended to suggest a novel mechanism of action, and further justify the search for alternative targets of ibogamine skeleton compounds.

Mechanism of hERG Channel Block by the Psychoactive Indole Alkaloid Ibogaine

Findings show that ibogaine blocks hERG channels from the cytosolic side either in its charged form alone or in company with its uncharged form and alters the currents by changing the relative contribution of channel states over time.

Ibogaine: Complex Pharmacokinetics, Concerns for Safety, and Preliminary Efficacy Measures

It is reported here that ibogaine significantly decreased craving for cocaine and heroin during inpatient detoxification and for short‐term stabilization of drug‐dependent persons as they prepare to enter substance abuse treatment.

Medication development of ibogaine as a pharmacotherapy for drug dependence.

A rising tolerance study using single administration of ibogaine for treatment of cocaine dependency is initiated to determine safety, pharmacokinetics and dose effects, and to identify relevant parameters of efficacy in cocaine-dependent patients.

Medication Development of Ibogaine as a Pharmacotherapy for Drug Dependence a

A rising tolerance study using single administration of ibogaine for the treatment of cocaine dependency is initiated to determine safety, pharmacokinetics and dose effects, and to identify relevant parameters of efficacy in cocaine‐dependent patients.

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Ibogaine and the inhibition of acetylcholinesterase.

Distribution of ibogaine and noribogaine in a man following a poisoning involving root bark of the Tabernanthe iboga shrub.

The tissue distribution of ibogaine and noribogaine, the main metabolite of ibogsaine, in a 48-year-old Caucasian male found dead at his home after a poisoning involving the ingestion of root bark from the shrub Tabernanthe iboga is reported.