Noribogaine stimulates naloxone-sensitive [35S]GTPgammaS binding.
Neuroreport – January 05, 1998
Source: PubMed
Summary
Noribogaine, a metabolite of the natural compound ibogaine, powerfully interacts with the brain's opioid system. Researchers investigated its effects on specific brain receptors, finding it significantly boosted activity in rat brain tissue by 170%. This effect was blocked by naloxone, confirming it targets opioid receptors. Its potency matched strong opioid drugs like morphine, while ibogaine itself showed no effect. This strong interaction may explain ibogaine's benefits for opioid withdrawal and reducing cravings.
Abstract
Noribogaine is formed in vivo by the O-demethylation of the indole alkaloid ibogaine. We report here that noribogaine acts as a full agonist at the mu-opioid receptor. Noribogaine-stimulated guanylyl 5'gamma-[35S]thio]triphosphate ([35S]GTPgammaS) was studied in rat thalamic membranes to measure activation of guanine nucleotide binding proteins (G-proteins) in the presence of excess GDP. Noribogaine caused a 170% increase above basal [35S]GTPgammaS binding at sub-micromolar effective concentrations (EC50) in a naloxone-sensitive manner, confirming that this effect was an opioid receptor-mediated process. The level of intrinsic activity for noribogaine in these assays was comparable to the full agonists DAMGO and morphine. In contrast, ibogaine had no significant effect on [35S]GTPgammaS binding over a similar concentration range. The efficacy of noribogaine as a full mu-opioid agonist may explain ibogaine's ability to block the acute signs of opiate withdrawal and its suppressive effects on morphine self-administration.