481-88-9Relevant articles and documents
A Single Administration of the Atypical Psychedelic Ibogaine or Its Metabolite Noribogaine Induces an Antidepressant-Like Effect in Rats
Carrera, Ignacio,Fabius, Sara,Havel, Vaclav,Reyes, Ana Laura,Sames, Dalibor,Scorza, Cecilia,Urbanavicius, Jessika,Prieto, José Pedro,Rodr?guez, Paola
, p. 1661 - 1672 (2020)
Anecdotal reports and open-label case studies in humans indicated that the psychedelic alkaloid ibogaine exerts profound antiaddictive effects. Ample preclinical evidence demonstrated the efficacy of ibogaine, and its main metabolite, noribogaine, in substance-use-disorder rodent models. In contrast to addiction research, depression-relevant effects of ibogaine or noribogaine in rodents have not been previously examined. We have recently reported that the acute ibogaine administration induced a long-term increase of brain-derived neurotrophic factor mRNA levels in the rat prefrontal cortex, which led us to hypothesize that ibogaine may elicit antidepressant-like effects in rats. Accordingly, we characterized behavioral effects (dose- and time-dependence) induced by the acute ibogaine and noribogaine administration in rats using the forced swim test (FST, 20 and 40 mg/kg i.p., single injection for each dose). We also examined the correlation between plasma and brain concentrations of ibogaine and noribogaine and the elicited behavioral response. We found that ibogaine and noribogaine induced a dose- and time-dependent antidepressant-like effect without significant changes of animal locomotor activity. Noribogaine's FST effect was short-lived (30 min) and correlated with high brain concentrations (estimated >8 μM of free drug), while the ibogaine's antidepressant-like effect was significant at 3 h. At this time point, both ibogaine and noribogaine were present in rat brain at concentrations that cannot produce the same behavioral outcome on their own (ibogaine ～0.5 μM, noribogaine ～2.5 μM). Our data suggests a polypharmacological mechanism underpinning the antidepressant-like effects of ibogaine and noribogaine.
Modulation of cellular calcium by sigma-2 receptors: Release from intracellular stores in human SK-N-SH neuroblastoma cells
Vilner, Bertold J.,Bowen, Wayne D.
, p. 900 - 911 (2007/10/03)
Human SK-N-SH neuroblastoma cells expressed sigma-1 and sigma-2 receptors with similar pharmacological profiles to those of rodent-derived tissues, although sigma-2 receptors exhibited some affinity differences that might suggest heterogeneity or species differences. Structurally diverse sigma ligands produced two types of increases in intracellular (cytosolic) Ca2+ concentration ([Ca2+](i)) in these cells. CB-64D, CB-64L, JL-II-147, BD737, LR172, BD1008, haloperidol, reduced haloperidol, and ibogaine all produced an immediate, dose-dependent, and transient rise in [Ca2+](i). Sigma-inactive compounds structurally similar to the most active sigma ligands and ligands for several neurotransmitter receptors produced little or no effect. The high activity of CB-64D and ibogaine (sigma-2-selective ligands) compared with the low activity of (+)-pentazocine and other (+)- benzomorphans (sigma-1-selective ligands), in addition to enantioselectivity for CB-64D over CB-64L, strongly indicated mediation by sigma-2 receptors. The effect of CB-64D and BD737 was blocked by the sigma antagonists BD1047 and BD1063, further confirming specificity as a receptor-mediated event. The transient rise in [Ca2+](i) occurred in the absence of extracellular Ca2+ and was completely eliminated by pretreatment of cells with thapsigargin. Thus, sigma-2 receptors stimulate a transient release of Ca2+ from the endoplasmic reticulum. Prolonged exposure of cells to sigma-receptor ligands resulted in a latent and sustained rise in Ca2+](i), with a pharmacological profile identical to that of the transient rise. This sustained rise in [Ca2+](i) was affected by neither the removal of extracellular Ca2+ nor thapsigargin pretreatment, suggesting latent sigma-2 receptor-induced release from thapsigargin-insensitive intracellular Ca2+ stores. Sigma-2 receptors may use Ca2+ signals in producing cellular effects.
