Effect of Ibogaine on the Various Sites of the NMDA Receptor Complex and Sigma Binding Sites in Rat Braina.
Annals of the New York Academy of Sciences May 1, 1998 DOI: 10.1111/j.1749-6632.1998.tb08239.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rat cortex and cerebellum membrane preparations |
| Intervention | ibogaine |
| Topics | Ibogaine |
| Citations | 20 |
| Key findings | Ibogaine binds to high- and low-affinity PCP sites in the cortex and only low-affinity sites in the cerebellum, has no affinity for NMDA receptor sites, and binds sigma-1 and sigma-2 sites with moderate affinity. |
Abstract
Although the alkaloid ibogaine is a potent hallucinogenic agent some indications suggest that it may be useful for the treatment of opioid and cocaine addiction. The neurochemical mechanism(s) underlying ibogaine effects remain unclear. In the present study we investigated the interaction of ibogaine with the phencyclidine (PCP) site located in the ionophore of the N-methyl-d-aspartate (NMDA) receptor complex, with the NMDA receptor binding site, and with sigma binding sites. In well-washed membrane preparations of rat cortex and cerebellum, the PCP sites were labeled with [3H]MK-801 or [3H]1-[1(2-theinyl)-cyclohexyl]-piperidine ([3H]TCP), and the NMDA receptor with [3H]-CGP 39653. The sigma-1 and sigma-2 binding site in rat cortex and cerebellum were labeled with [3H]pentazocine and [3H]1,3-di-o-tolyl-guanidine ([3H]DTG), respectively. Results indicated that ibogaine interacts with high- and low-affinity PCP binding sites in the cortex: Ki(H) = 0.01-0.05 μM; Ki(L) = 2-4μM, and only with low-affinity sites in the cerebellum: Ki = 2-4, μM. In contrast, ibogaine (>100 μM) had no affinity for [3H]-CGP 39653 binding sites (cortex and cerebellum). The affinity of ibogaine for sigma-1 and -2 binding sites in cortex and cerebellum ranged from 1.5-3μM. Since NMDA receptor antagonists (e.g., MK-801) are thought to attenuate opioid withdrawal symptoms and cocaine sensitization, it is possible that binding of ibogaine to the PCP sites contributes to its potential 'endabuse' properties. In turn, ibogaine interaction with sigma binding sites may be associated with its adverse effects.
Comparable studies
Other experimental studies on ibogaine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ibogaine, a noncompetitive inhibitor of serotonin transport, acts by stabilizing the cytoplasm-facing state of the transporter. In vitro (SERT) | 2007 | Laboratory study | |
| Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies. | 1992 | Laboratory study | |
| The mechanistic basis for noncompetitive ibogaine inhibition of serotonin and dopamine transporters. | 2012 | Experimental study | |
| Identification of a primary metabolite of ibogaine that targets serotonin transporters and elevates serotonin. | 1995 | Experimental study | |
| Ibogaine and its congeners are sigma 2 receptor-selective ligands with moderate affinity. | 1995 | Laboratory study |
Citations in the library
Cited by 6
- Unique and potent effects of acute ibogaine on zebrafish: the developing utility of novel aquatic models for hallucinogenic drug research. Behavioural Brain Research 2013
- The effects of ibogaine on dopamine and serotonin transport in rat brain synaptosomes. Brain Research Bulletin April 1, 1999
- Understanding the Healing Potential of Ibogaine through a Comparative and Interpretive Phenomenology of the Visionary Experience Anthropology of Consciousness March 1, 2018
- Ibogaine and Noribogaine: Comparing Parent Compound to Metabolite CNS Drug Reviews September 1, 2000
- The visionary cure of the addiction war? Ibogaine: social context, subcultural identity, and implications for drug policy Drugs and Alcohol Today June 17, 2011
and 1 more in the library
Cites 9
- 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
- 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
- Receptor binding profile suggests multiple mechanisms of action are responsible for ibogaine's putative anti-addictive activity. Psychopharmacology April 1, 1995
- Ibogaine and its congeners are sigma 2 receptor-selective ligands with moderate affinity. European Journal of Pharmacology June 6, 1995
and 4 more in the library