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Properties of ibogaine and its principal metabolite (12-hydroxyibogamine) at the MK-801 binding site of the NMDA receptor complex
Open accessAbstract
The putative anti-addiction alkaloid ibogaine and its principal metabolite 12-hydroxyibogamine appear to act at the (+)-5 methyl-10,11,dihydro-5H- dibenzo[a,d]cycloheten-5-10-imine maleate (MK-801) binding site in the N-methyl-D-aspartate (NMDA)-receptor cation channel. This conclusion is based on findings that both compounds competitively displaced specific [3H]MK-801 binding to membranes from postmortem human caudate and cerebellum and from frog spinal cord. Ibogaine was 4-6-fold more potent than its metabolite and both compounds were less potent (50-1000-fold) than MK-801 binding to the NMDA receptor. In addition, ibogaine (100 microM) and 12-hydroxyibogamine (1 mM) blocked (85-90% of control) the ability of NMDA (100 microM, 5 s) to depolarize frog motoneurons in the isolated frog spinal cord. The prevention of NMDA-depolarizations in frog motoneurons showed use-dependency and was very similar to the block produced by MK-801. In view of the abilities of MK-801 to affect the responses to addictive substances in pre-clinical investigations, our results are compatible with the idea that the ability of ibogaine and 12-hydroxyibogamine to interrupt drug-seeking behavior may, in part, result from their actions at the MK-801 binding site.
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Ibogaine had some affinity for NMDA receptors, displacing [3H]MK801 from caudate membranes with an IC50 of 5 μM.
“Ibogaine (17) also had some affinity for NMDA receptors, displacing [3H]MK801 from caudate membranes with an IC50 of 5 µM [61]”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [61]
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Cited by
Sorted by citations
Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans.
Cumming, P., Scheidegger, M., Dornbierer, D., Palner, M., Quednow, B. B., & Martin-Soelch, C. (2021) · Molecules · doi:10.3390/molecules26092451 · Cited by 43
“Ibogaine (17) also had some affinity for NMDA receptors, displacing [3H]MK801 from caudate membranes with an IC50 of 5 μM [61], which may account for its dissociative side effects.”
Background
Metadata
- Authors
- Mash, D. C., Staley, J. K., Pablo, J. P., Holohean, A. M., Hackman, J. C., & Davidoff, R. A.
- Affiliations
- University of Miami (US)
- United States Department of Veterans Affairs (US)
- Corresponding author
- Davidoff, R.A.
- ORCID
- Mash, D.C.
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 1995-06
- Volume
- 192
- Issue
- 1
- Pages
- 53-56
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W1994849988
- Cited by
- 80
- References
- 0
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 7 · 2021: 3 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 1 · 2015: 2
- FWCI
- 11.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuroscience Letters (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ns017577-14)
- National Institute of Neurological Disorders and Stroke (NS-17577)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Alkaloids: synthesis and pharmacology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Keywords
- ibogaine, NMDA receptor, competitive binding, caudate nucleus, cerebellum, spinal motoneurons, use-dependent block, drug-seeking behavior
- MeSH terms
- Adult, Animals, Binding, Competitive, Dose-Response Relationship, Drug, Humans, Ibogaine, Male, Motor Activity, Rana pipiens, Receptors, N-Methyl-D-Aspartate, Dizocilpine Maleate
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