Frontiers in pharmacology
January 1, 2019
Soledad Marton, Bruno González, Sebastián Rodríguez-bottero et al.
71 citations
A single injection of ibogaine in rats increased the expression of neurotrophic factors in brain regions containing dopamine neurons, with effects depending on dose and brain area. At 24 hours, the higher dose (40 mg/kg) selectively raised GDNF in the ventral tegmental area and substantia nigra, while both doses boosted BDNF transcripts in the nucleus accumbens, substantia nigra, and prefrontal cortex. NGF mRNA increased across all regions after the higher dose. Protein levels showed GDNF rise only in the ventral tegmental area at the higher dose, and proBDNF increased in the nucleus accumbens for both doses. These changes may help explain ibogaine's reported ability to reduce drug-seeking behavior.
ACS omega
July 6, 2021
Bruno González, Catherine Fagúndez, Alejandro Peixoto de Abreu Lima et al.
18 citations
An optimized process extracts voacangine from Voacanga africana root bark using a direct acetone-based procedure, yielding approximately 0.8% of the dried root bark weight. The major alkaloids isolated are iboga-vobasinyl dimers, such as voacamine and voacamidine, which constitute about 3.7% of the bark. Because these dimers contain the voacangine moiety, a further optimized cleavage step produces additional voacangine at about 50% isolated molar yield. Applying both extraction and dimer cleavage nearly doubles the total voacangine obtained from the plant material compared to direct extraction alone.
International journal of molecular sciences
January 5, 2024
Sofía Villalba, Bruno González, Stephanie Junge et al.
9 citations
Noribogaine, the primary metabolite of ibogaine, produces sexually dimorphic effects in mice, with some responses depending on the 5-HT2A receptor. A single 40 mg/kg dose reduced locomotion in male but not female wild-type mice. Gene expression of immediate early genes and glutamate receptors differed by sex and genotype. 5-HT2A receptor mRNA increased in the medial prefrontal cortex after noribogaine at 10 mg/kg in males and 40 mg/kg in females. Electrophysiology showed that 40 mg/kg reduced NMDA-mediated postsynaptic current density in layer V pyramidal neurons of the medial prefrontal cortex only in male wild-type mice, an effect absent in 5-HT2A receptor knockout males and all females. The genetic removal of the 5-HT2A receptor blunted noribogaine's effects on NMDA synaptic transmission.
Journal of natural products
June 23, 2023
Bruno González, Nicolás Veiga, Gonzalo Hernández et al.
7 citations
The iboga alkaloids, such as ibogaine and voacangine, are promising scaffolds for developing drugs to treat neuropsychiatric disorders. This work examines how these molecules react under oxidation with dioxygen, peroxo compounds, and iodine. The C16-carboxymethyl ester group in voacangine makes the molecule more stable toward oxidation than ibogaine, particularly in the indole ring, where 7-hydroxy- or 7-peroxy-indolenines form. However, the ester increases reactivity at the isoquinuclidinic nitrogen, leading to C3-oxidized products via regioselective iminium formation. Density functional theory calculations explain this differential reactivity. Additionally, NMR experiments and theoretical calculations revise the absolute stereochemistry at C7 in voacangine's 7-hydroxyindolenine to S, correcting earlier reports of R configuration.
Journal of the American Chemical Society
December 26, 2025
Christopher Hwu, Václav Havel, Xavier Westergaard et al.
2 citations
Ibogaine and its main metabolite noribogaine inhibit the vesicular monoamine transporter 2 (VMAT2) with submicromolar potency, as shown in cell-based assays and two-photon microscopy of mouse brain synaptic vesicle clusters. Noribogaine also induces partial serotonin release from synaptic vesicles and binds VMAT2 at a distinct site from the established inhibitor dihydrotetrabenazine. These compounds additionally inhibit plasma membrane monoamine transporters, prominently the serotonin transporter (SERT), and a novel target, organic cation transporter 2 (OCT2). Several iboga analogs display dual inhibition of VMAT2 and SERT with comparable potencies, termed "Synaptic Reuptake Inhibitors" (SynRIs). This profile explains why ibogaine and noribogaine do not induce catalepsy, unlike other VMAT2 inhibitors, and illustrates the complex "matrix pharmacology" of iboga compounds.
ChemRxiv
October 29, 2018
Soledad Marton, Bruno González, Sebastián Rodríguez et al.
Ibogaine, a psychedelic alkaloid, alters the expression of three neurotrophic factors—GDNF, BDNF, and NGF—in rat brain regions containing dopamine neurons. A single injection of 20 or 40 mg/kg ibogaine increased expression of these factors after 24 hours in a dose- and region-specific manner. The higher dose selectively raised GDNF in the ventral tegmental area and substantia nigra. Both doses increased BDNF in the nucleus accumbens, substantia nigra, and prefrontal cortex, while the higher dose also raised BDNF in the ventral tegmental area. NGF increased in all regions after the higher dose. Mature GDNF protein rose in the ventral tegmental area, and proBDNF increased in the nucleus accumbens. These changes may contribute to ibogaine's anti-addictive properties.