hERG Blockade by Iboga Alkaloids

@article{Alper2015hERGBB,
  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},
  year={2015},
  volume={16},
  pages={14-22}
}
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.

The root extract of Carapichea ipecacuanha inhibited human ether-a-go- go-related gene channel currents and raised further questions regarding the safety and over-the-counter appropriateness of these herbal products.

DARK Classics in Chemical Neuroscience: Ibogaine.

Structural-activity studies led to the isolation of the ibogaine analog 18-methoxycoronaridine (18-MC), an α3β4 nicotinic receptor modulator that retains ibogane's anticraving properties with few or no adverse effects.

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.

In an in vitro screening of herbal materials for hERG blockers using an automated two-microelectrode voltage clamp assay on Xenopus oocytes, an alkaloid fraction of Nelumbo nucifera Gaertn.

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.

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