High affinity ibogaine binding to a mu opioid agonist site.
Life Sciences 1995 DOI: 10.1016/0024-3205(95)02171-e (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Laboratory experiment Peer reviewed |
|---|---|
| Population | Mouse forebrain tissue |
| Topics | Ibogaine |
| Citations | 29 |
| Key findings | Ibogaine acts as an agonist at the mu opioid receptor with a Ki value of about 130 nM, which may explain its antinociceptive effects and reduction of opioid withdrawal and drug-seeking behavior. |
Abstract
The naturally occurring indole alkaloid ibogaine is of interest because of its reported ability to block drug seeking behavior for extended periods. The compound also potentiates morphine-induced analgesia in mice and reduces certain naltrexone-precipitated withdrawal signs in morphine-dependent rats. Although these results might suggest ibogaine interaction with opioid receptors, previous receptor binding studies (Brain Res. 571:242-247, 1980) found that ibogaine had a Ki value of only 2 microM for the kappa opioid receptor and was virtually inactive in blocking mu and delta receptor binding (Ki > 100 microM). The present investigation of ibogaine interaction with the mu opioid receptor from mouse forebrain labeled with [3H]-naloxone, however, yielded significantly more potent mu opioid Ki values. LIGAND analysis indicated that the data were best fit by a two site binding model, with Ki values of about 130 nM and 4 microM, reflecting ibogaine recognition of different agonist affinity states of the receptor. Inclusion of 100 mM NaCl in the assay to induce the agonist low affinity state of the receptor, reduced ibogaine's inhibition of [3H]-naloxone binding. These results suggest that ibogaine is an agonist at the mu opioid receptor with a Ki value of about 130 nM, potentially explaining ibogaine's antinociceptive effects as well as its reported reduction of opioid withdrawal symptoms and attenuation of drug seeking behavior.
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 19
- Unique and potent effects of acute ibogaine on zebrafish: the developing utility of novel aquatic models for hallucinogenic drug research. Behavioural Brain Research 2013
- Medication Development of Ibogaine as a Pharmacotherapy for Drug Dependencea. Annals of the New York Academy of Sciences May 1, 1998
- Ibogaine: a potent noncompetitive blocker of ganglionic/neuronal nicotinic receptors. Molecular Pharmacology 1997
- Ibogaine and cocaine abuse: pharmacological interactions at dopamine and serotonin receptors. Brain Research Bulletin 1997
- Noribogaine stimulates naloxone-sensitive [35S]GTPgammaS binding. Neuroreport January 5, 1998
and 14 more in the library
Cites 11
- Effects and aftereffects of ibogaine on morphine self-administration in rats. European Journal of Pharmacology April 3, 1991
- Inhibitory effects of ibogaine on cocaine self-administration in rats. European Journal of Pharmacology September 14, 1993
- Ibogaine possesses a selective affinity for sigma 2 receptors. Life Sciences 1995
- Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies. Brain Research February 7, 1992
- Effects of ibogaine on acute signs of morphine withdrawal in rats: independence from tremor. Neuropharmacology May 1, 1992
and 6 more in the library