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.
Comparable studies
Other preclinical and animal studies on ibogaine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Noncompetitive Functional Inhibition at Diverse, Human Nicotinic Acetylcholine Receptor Subtypes by Bupropion, Phencyclidine, and Ibogaine TE671/RD cells (human muscle-type nAChR) and SH-SY5Y neuroblastoma cells (human... | 1999 | In vitro study | |
| Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Ibogaine- or harmaline-treated rats | 1993 | Experimental animal study | |
| Effects and aftereffects of ibogaine on morphine self-administration in rats. Rats | 1991 | Preclinical experimental study | |
| Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum. Rats | 1994 | Experimental study | |
| Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption Rats | 2005 | Experimental study |
Citations in the library
Cited by 16
- Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures. Annals of the New York Academy of Sciences September 1, 2000
- Medication Development of Ibogaine as a Pharmacotherapy for Drug Dependencea. Annals of the New York Academy of Sciences May 1, 1998
- Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. A narrative review. Human & Experimental Toxicology March 1, 2008
- Changes in Withdrawal and Craving Scores in Participants Undergoing Opioid Detoxification Utilizing Ibogaine. Journal of Psychoactive Drugs 2018
- Ascending-dose study of noribogaine in healthy volunteers: pharmacokinetics, pharmacodynamics, safety, and tolerability. The Journal of Clinical Pharmacology February 1, 2015
and 11 more in the library
Cites 3
- A preliminary investigation of ibogaine: case reports and recommendations for further study. Journal of Substance Abuse Treatment 1994
- High affinity ibogaine binding to a mu opioid agonist site. Life Sciences 1995
- Effects of ibogaine and noribogaine on the antinociceptive action of mu-, delta- and kappa-opioid receptor agonists in mice. Brain Research March 28, 1997