The effect of ibogaine on Sigma- and NMDA-receptor-mediated release of [3H]dopamine.
Henry Sershen, Audrey Hashim, Ábel Lajtha
Brain Research Bulletin 1996 DOI: 10.1016/0361-9230(96)00039-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | Striatal tissue from C57BL/6By mice |
| Intervention | Ibogaine |
| Dose | 1 µM, 10 µM |
| Topics | Ibogaine |
| Citations | 19 |
| Key findings | Ibogaine inhibits NMDA- and sigma-receptor-mediated dopamine release in mouse striatum, and may also remove tonic kappa-opioid inhibition of dopamine release. |
Abstract
The indole alkaloid ibogaine has been suggested to have potential for inhibiting dependency on stimulant drugs. Radioligand binding studies have suggested possible multisite actions of ibogaine: affinity at the kappa-opioid, NMDA, and sigma receptors, with effects on dopamine (DA) release. To further investigate the multiplicity of sites of action of ibogaine and the presynaptic regulation of the DA release, the effect of ibogaine on NMDA- and sigma-receptor-mediated efflux of [3H]DA was measured in striatal tissue from C57BL/6By mice. Striatal tissue was incubated in vitro with [3H]DA and the effect on DA release was measured. Both NMDA (25 microM) alone increased the efflux of DA. (+/)-Pentazocine (100 nM) did not inhibit the NMDA-evoked release. MK-801 (5 microM) completely inhibited the NMDA-evoked release and inhibited the (+/-)-pentazocine-evoked release by 49%. Ibogaine (10 microM) itself increased the efflux of DA; at 1 microM it was without effect. Ibogaine (1 microM) inhibited the NMDA-evoked release of DA by 31% and inhibited the (+/-)-pentazocine-evoked release by 48%. In addition, the level of basal release of DA obtained after the NMDA- or (+/)-pentazocine-evoked-release remained higher in the tissue exposed to ibogaine throughout. The results suggest that sigma receptors can regulate the release of DA, along with an action at the NMDA receptor. We previously reported action of ibogaine at the kappa-opioid site. The elevated basal release of DA in the presence of ibogaine after NMDA- or (+/-)-pentazocine-evoked release may reflect the ibogaine-induced removal of the tonically active kappa-opioid system that acts presynaptically to reduce dopamine release. The kappa-opioid system also appears to be inhibitory on both the NMDA and sigma receptors.
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 13
- Ibogaine: a potent noncompetitive blocker of ganglionic/neuronal nicotinic receptors. Molecular Pharmacology 1997
- A case report SPECT study and theoretical rationale for the sequential administration of ibogaine and 5-MeO-DMT in the treatment of alcohol use disorder. Progress in Brain Research 2018
- Modified ibogaine fragments: synthesis and preliminary pharmacological characterization of 3-ethyl-5-phenyl-1,2,3,4,5, 6-hexahydroazepino[4,5-b]benzothiophenes. Journal of Medicinal Chemistry November 5, 1998
- Ibogaine and cocaine abuse: pharmacological interactions at dopamine and serotonin receptors. Brain Research Bulletin 1997
- The potential of psychedelics for the treatment of Alzheimer's disease and related dementias. European Neuropsychopharmacology November 1, 2023
and 8 more in the library
Cites 13
- 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
- Interactions between ibogaine, a potential anti-addictive agent, and morphine: an in vivo microdialysis study. European Journal of Pharmacology June 18, 1991
- The putative anti-addictive drug ibogaine is a competitive inhibitor of [3H]MK-801 binding to the NMDA receptor complex. Psychopharmacology May 1, 1994
- Radioligand-binding study of noribogaine, a likely metabolite of ibogaine. Brain Research March 27, 1995
and 8 more in the library