Noribogaine stimulates naloxone-sensitive [35S]GTPgammaS binding.

Noribogaine, a metabolite produced in the body from the natural compound ibogaine, acts as a full agonist at the mu-opioid receptor. In rat thalamic membranes, noribogaine stimulated a 170% increase above basal G-protein activation at sub-micromolar concentrations, an effect blocked by naloxone, confirming opioid receptor involvement. Its intrinsic activity matched that of the full agonists DAMGO and morphine. Ibogaine itself had no significant effect. This full mu-opioid agonist efficacy may explain ibogaine's ability to block acute opiate withdrawal and reduce morphine self-administration.

Study at a glance

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.