Noribogaine generalization to the ibogaine stimulus: correlation with noribogaine concentration in rat brain.
C Zubaran, M Shoaib, I P Stolerman, John Pablo, Deborah C. Mash
Neuropsychopharmacology July 1, 1999 DOI: 10.1016/s0893-133x(99)00003-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Ibogaine Noribogaine Dizocilpine U50 488 |
| Dose | 10 mg/kg i.p. ibogaine, 0.08 mg/kg i.p. dizocilpine, 5 mg/kg i.p. U50,488 |
| Topics | Ibogaine |
| Keywords | Psychoactive compound Alkaloid Drug metabolite Neuropharmacology Brain responses Drug action Psychopharmacology Stimulus effects Drug metabolism Biotransformation Animal studies Preclinical research Rat model |
| Citations | 31 |
| Key points | The metabolite noribogaine appears to mediate the discriminative stimulus effect of ibogaine in rats, likely without NMDA antagonist or kappa-opioid agonist properties. |
Abstract
The discriminative stimulus effects of ibogaine and noribogaine in rats have been examined in relation to their concentrations in blood plasma and brain regions and to receptor systems through which they have been proposed to act. Rats were trained to discriminate ibogaine (10 mg/kg i.p.), the NMDA antagonist dizocilpine (0.08 mg/kg i.p.) or the kappa-opioid agonist U50,488 (5 mg/kg i.p.) from vehicle in a standard two-lever operant conditioning procedure with a tandem VI-FR schedule of food reinforcement. Only rats trained on ibogaine generalized to noribogaine, which was approximately twice as potent as the parent compound. Noribogaine was detected in plasma and brain after administration of ibogaine and noribogaine. At the ED50 doses for the discriminative effect, the estimated concentrations of noribogaine in plasma, cerebral cortex, and striatum were similar regardless of whether ibogaine or noribogaine was administered. The findings suggest that the metabolite noribogaine may be devoid of NMDA antagonist and kappa-opioid agonist discriminative effects and that it may play a major role in mediating the discriminative stimulus effect of ibogaine.
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 23
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Ibogaine in the treatment of substance dependence. Current Drug Abuse Reviews March 1, 2013
- Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. A narrative review. Human & Experimental Toxicology March 1, 2008
- Ibogaine Administration Modifies GDNF and BDNF Expression in Brain Regions Involved in Mesocorticolimbic and Nigral Dopaminergic Circuits. Frontiers in Pharmacology 2019
- In Vivo Neurobiological Effects of Ibogaine and Its O-Desmethyl Metabolite, 12-Hydroxyibogamine (Noribogaine), in Rats Journal of Pharmacology and Experimental Therapeutics May 1, 2001
and 18 more in the library
Cites 22
- Inhibitory effects of ibogaine on cocaine self-administration in rats. European Journal of Pharmacology September 14, 1993
- A preliminary investigation of ibogaine: case reports and recommendations for further study. Journal of Substance Abuse Treatment 1994
- Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies. Brain Research February 7, 1992
- Interactions between ibogaine, a potential anti-addictive agent, and morphine: an in vivo microdialysis study. European Journal of Pharmacology June 18, 1991
- 18-Methoxycoronaridine, a non-toxic iboga alkaloid congener: effects on morphine and cocaine self-administration and on mesolimbic dopamine release in rats. Brain Research May 6, 1996
and 17 more in the library