Ibogaine block of the NMDA receptor: in vitro and in vivo studies.
K Chen, T G Kokate, S D Donevan, F I Carroll, M A Rogawski
Neuropharmacology April 1, 1996 DOI: 10.1016/0028-3908(96)84107-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Cultured rat hippocampal neurons and mouse model |
| Intervention | Ibogaine |
| Dose | 3.1 μM (IC50 in vitro), 31 mg/kg (ED50 in vivo) |
| Topics | Ibogaine |
| Citations | 55 |
| Key findings | Ibogaine is an open-channel NMDA receptor antagonist that blocks NMDA-induced currents in vitro and protects mice against NMDA-mediated seizures and lethality. |
Abstract
Ibogaine is an hallucinogenic indole alkaloid claimed to have anti-addictive properties. Although its mechanism of action is unknown, binding studies have indicated that the drug may interact with N-methyl-D-aspartate (NMDA) receptors. We further investigated the nature of the interaction between ibogaine and NMDA receptors in voltage clamp and binding studies, and sought to confirm that the drug has NMDA receptor blocking activity in vivo. In whole-cell recordings from cultured rat hippocampal neurons, ibogaine caused a slow, concentration-dependent block of NMDA-induced currents (IC50, 3.1 microM at -60 mV). In contrast, ibogaine failed to affect either kainate- or gamma-aminobutyric acid-evoked currents. The blockade of NMDA currents was use- and voltage-dependent, and the long lasting ibogaine block could be occluded by co-application of Mg2+. Ibogaine also inhibited equilibrium [3H]dizocilpine binding to NMDA receptors in rat forebrain membranes (IC50, 3.2 microM). We conclude that ibogaine is an open channel NMDA receptor antagonist. Administration of ibogaine to mice resulted in complete protection in the maximal electroshock test (ED50, 31 mg/kg, i.p.) and partial protection against NMDA-induced lethality, confirming that ibogaine can block NMDA receptors in vivo.
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 29
- Treatment of acute opioid withdrawal with ibogaine. American Journal on Addictions 1999
- Antagonism of alpha 3 beta 4 nicotinic receptors as a strategy to reduce opioid and stimulant self-administration. European Journal of Pharmacology March 1, 2002
- Unique and potent effects of acute ibogaine on zebrafish: the developing utility of novel aquatic models for hallucinogenic drug research. Behavioural Brain Research 2013
- Fatalities temporally associated with the ingestion of ibogaine. Journal of Forensic Sciences March 1, 2012
- Ibogaine and addiction in the animal model, a systematic review and meta-analysis. Translational Psychiatry May 31, 2016
and 24 more in the library
Cites 15
- Hallucinogens of Plant Origin Science January 17, 1969
- Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Neuroscience July 1, 1993
- 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
- A preliminary investigation of ibogaine: case reports and recommendations for further study. Journal of Substance Abuse Treatment 1994
and 10 more in the library