title: Noribogaine stimulates naloxone-sensitive [35S]GTPgammaS binding.
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.
authors.affiliation: Department of Neurology, University of Miami School of Medicine, FL 33136, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Pablo
authors.forename: D C
authors.initials: DC
authors.lastname: Mash
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism*; D007050:Ibogaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016015:Logistic Models; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists; D013268:Stimulation, Chemical; D013462:Sulfur Radioisotopes
chemical_list: D004745:Enkephalins; D017450:Receptors, Opioid, mu; D013462:Sulfur Radioisotopes; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D007050:Ibogaine; C094385:noribogaine