Structure-activity relationship of ibogaine analogs interacting with nicotinic acetylcholine receptors in different conformational states.
Hugo R Arias, Dominik Feuerbach, Katarzyna M Targowska-Duda, Krzysztof Jozwiak
The international journal of biochemistry & cell biology September 1, 2011 DOI: 10.1016/j.biocel.2011.05.011 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Interventions | 18-methoxycoronaridine ibogaine catharanthine |
| Topics | Ibogaine |
| Keywords | Ibogaine analogs Nicotinic acetylcholine receptors Receptor binding Structure-activity relationship |
| Citations | 10 |
| Key findings | The size of the binding site for ibogaine analogs, located between the serine and nonpolar rings and shared with TCP, is an important structural feature for binding and inducing desensitization. |
Abstract
The interaction of ibogaine analogs with nicotinic acetylcholine receptors (AChRs) in different conformational states was studied by functional and structural approaches. The results established that ibogaine analogs: (a) inhibit (±)-epibatidine-induced Ca²⁺ influx in human embryonic muscle AChRs with the following potency sequence (IC(50) in μM): (±)-18-methylaminocoronaridine (5.9±0.3)∼(±)-18-methoxycoronaridine (18-MC) (6.8±0.8)>(-)-ibogaine (17±3)∼(+)-catharanthine (20±1)>(±)-albifloranine (46±13), (b) bind to the [³H]TCP binding site with higher affinity when the Torpedo AChR is in the desensitized state compared to that in the resting state. Similar results were obtained using [³H]18-MC. These and docking results suggest a steric interaction between TCP and ibogaine analogs for the same site, (c) enhance [³H]cytisine binding to resting but not to desensitized AChRs, with desensitizing potencies (apparent EC₅₀) that correlate very well with the pK(i) values in the desensitized state, and (d) there are good bilinear correlations between the ligand molecular volumes and their affinities in the desensitized and resting states, with an optimal volume of ∼345 ų for the ibogaine site. These results indicate that the size of the binding sites for ibogaine analogs, located between the serine and nonpolar rings and shared with TCP, is an important structural feature for binding and for inducing desensitization.
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 5
- Reactivity of the Iboga Skeleton: Oxidation Study of Ibogaine and Voacangine. Journal of Natural Products June 23, 2023
- Psychedelics and Autism Therapy: A Review of Current Research and Future Directions Current Issues in Molecular Biology April 18, 2026
- The iboga enigma: the chemistry and neuropharmacology of iboga alkaloids and related analogs. Natural Product Reports March 4, 2021
- Selectivity of coronaridine congeners at nicotinic acetylcholine receptors and inhibitory activity on mouse medial habenula. The international journal of biochemistry & cell biology October 16, 2017
- Coronaridine congeners inhibit human α3β4 nicotinic acetylcholine receptors by interacting with luminal and non-luminal sites. The international journal of biochemistry & cell biology May 27, 2015
Cites 10
- Noncompetitive Functional Inhibition at Diverse, Human Nicotinic Acetylcholine Receptor Subtypes by Bupropion, Phencyclidine, and Ibogaine Journal of Pharmacology and Experimental Therapeutics 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
- 18-Methoxycoronaridine (18-MC) and ibogaine: comparison of antiaddictive efficacy, toxicity, and mechanisms of action. Annals of the New York Academy of Sciences September 1, 2000
- Ibogaine: a potent noncompetitive blocker of ganglionic/neuronal nicotinic receptors. Molecular Pharmacology 1997
- Interaction of ibogaine with human alpha3beta4-nicotinic acetylcholine receptors in different conformational states. The international journal of biochemistry & cell biology September 1, 2010
and 5 more in the library