Presenter

Ignacio Carrera

Ibogaine as an inspiring molecular structure for the development of novel GDNF releasers as new anti-addictive agents

Ibogaine’s anti-addictive properties have been the focus of intensive research in the past years. Recent work has suggested that Ibogaine´s effects on the brain could be related to the release of Glial Cell Line-Derived Neurotrophic Factor (GDNF) in a midbrain region known as Ventral Tegmental Area (VTA). GDNF is a protein that has been implied in the attenuation of biochemical and behavioral changes observed upon exposure of rodents to drugs of abuse like psychostimulants, opiods and ethanol, and thus represents a potential target for treatment of addiction.

In this work, we aimed to prepare different ibogaine analogues in order to search for molecules with enhanced GDNF releasing properties. Inspired by the ibogaine’s molecular skeleton and the state of the art, we have prepared several N-indolylethyl-isoquinuclidines using enantioselective synthetic strategies. We tested these compounds in vitro, using C6 cells and also astrocytes from primary cultures, to assay their GDNF releasing potential. Preliminary results show that some derivatives exhibit better GDNF releasing capabilities than ibogaine itself, constituting promising potential candidates as anti-addictive substances.