Structurally modified ibogaine analogs exhibit differing affinities for NMDA receptors.
Richard T. Layer, Phil Skolnick, C M Bertha, Upul K. Bandarage, Martin E. Kuehne, Piotr Popik
European Journal of Pharmacology August 8, 1996 DOI: 10.1016/0014-2999(96)00304-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Morphine-dependent mice |
| Interventions | ibogaine O-desmethylibogaine O-t-butyl-O-desmethylibogaine |
| Topics | Ibogaine |
| Citations | 48 |
| Key findings | Ibogaine was the most potent NMDA receptor antagonist among the tested analogs and, unlike its metabolites, reduced naloxone-precipitated withdrawal in morphine-dependent mice. |
Abstract
Based on both preclinical findings and anecdotal evidence in man, the psychoactive indole alkaloid ibogaine has been suggested to have anti-addictive properties. Previous studies indicate that blockade of NMDA receptors may mediate at least some of the putative anti-addictive actions of ibogaine. The potencies of a series of ibogaine analogs to inhibit (+)-[3-3H]5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10- imine ([3H]MK-801) binding to NMDA receptors were examined. This series of analogs included the putative ibogaine metabolite O-desmethylibogaine, its metabolism resistant analog O-t-butyl-O-desmethylibogaine, the iboga alkaloids (+/-)-ibogamine, (+/-)-coronaridine, tabernanthine, harmaline, and the indolotropanes endo-3-(1-methylindol-2-yl)-8-methyl-8-azabicyclo[3.2.1]loctane (RS 075194-190), exo-3-(1-methylindol-2-yl)-8-methyl-8-azabicyclo[3.2.1]octane (RS 075237-190), and endo-3-(indol-2-yl)-8-methyl-8-azabicyclo[3.2.1]octane (RS 025989-190). Among these compounds, ibogaine was the most potent inhibitor of [3H]MK-801 binding (Ki = approximately 1.2 microM), whilst the compounds with the greatest structural similarity to ibogaine, O-desmethylibogaine and O-t-butyl-O-desmethylibogaine were less potent (Ki = approximately 5.5 and 179.0 microL, respectively). In morphine-dependent mice, ibogaine, but not O-desmethylibogaine or O-t-butyl-O-desmethylibogaine, attenuated naloxone precipitated withdrawal jumping. These findings are consistent with the hypothesis that inhibition of the expression of morphine dependence by ibogaine is related to its NMDA receptor antagonist properties.
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 27
- Treatment of acute opioid withdrawal with ibogaine. American Journal on Addictions 1999
- The ibogaine medical subculture. Journal of Ethnopharmacology January 4, 2008
- Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes. The American Journal of Drug and Alcohol Abuse 2018
- Ibogaine in the treatment of substance dependence. Current Drug Abuse Reviews March 1, 2013
- Fatalities temporally associated with the ingestion of ibogaine. Journal of Forensic Sciences March 1, 2012
and 22 more in the library
Cites 19
- Effects and aftereffects of ibogaine on morphine self-administration in rats. European Journal of Pharmacology April 3, 1991
- 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. Brain Research September 19, 1994
- 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
and 14 more in the library