Noribogaine stimulates naloxone-sensitive [35S]GTPgammaS binding.
Neuroreport January 5, 1998 DOI: 10.1097/00001756-199801050-00022 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro pharmacological study Peer reviewed |
|---|---|
| Population | Rat thalamic membranes |
| Interventions | Noribogaine ibogaine DAMGO morphine |
| Dose | sub-micromolar effective concentrations (EC50) |
| Topics | Ibogaine |
| Keywords | Ibogaine metabolite Active metabolite Opioid system Opioid receptors Brain receptors Central nervous system Mechanism of action Drug action Receptor binding Neuropharmacology Potency Opioid withdrawal Addiction treatment Craving reduction Substance abuse Therapeutic potential Natural compound Parent drug Precursor |
| Citations | 27 |
| Key points | Noribogaine acts as a full mu-opioid receptor agonist, with efficacy comparable to DAMGO and morphine, while ibogaine shows no significant effect. |
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.