Noribogaine is a G-protein biased κ-opioid receptor agonist.
Neuropharmacology December 1, 2015 Emeline L Maillet, Nicolas Milon, Mari D Heghinian et al. 59 citations
Noribogaine, the main human metabolite of the anti-addictive substance ibogaine, reaches brain concentrations up to 20 μM after a therapeutic dose. Binding experiments and computational simulations indicate it may bind to the orthosteric morphinan site of opioid receptors. Noribogaine is a weak mu opioid receptor antagonist (Ke=20 μM at both G-protein and β-arrestin pathways) but a G-protein biased kappa opioid receptor agonist: 75% as efficacious as dynorphin A at stimulating GDP-GTP exchange (EC50=9 μM) yet only 12% as efficacious at recruiting β-arrestin. It also functionally inhibits dynorphin-induced kappa β-arrestin recruitment (IC50=1 μM), more potent than its G-protein agonism.