Non-hallucinogenic compounds derived from iboga alkaloids alleviate neuropathic and visceral pain in mice through a mechanism involving 5-HT2A receptor activation.
Hugo R Arias, L. Micheli, Deborah Rudin, Ophélie Bento, Saskia Borsdorf, C. Ciampi, Philippe Marin, Evgeni Ponimaskin, Dina Manetti, M. Romanelli, C. Ghelardini, Matthias E. Liechti, L. di Cesare Mannelli
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie June 17, 2024 DOI: 10.1016/j.biopha.2024.116867 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study using mouse models Peer reviewed |
|---|---|
| Population | Mice with neuropathic pain (Chronic Constriction Injury) or visceral pain (dextrane sulfate sodium-induced colitis) |
| Interventions | tabernanthalog (TBG) ibogainalog (IBG) ibogaminalog (DM506) |
| Topics | Ibogaine Serotonin |
| Citations | 14 |
| Key findings | The anti-hypersensitivity activity of ibogalogs in mice is mediated by a mechanism involving 5-HT2A receptor activation. |
Abstract
The aim of this study was to determine the anti-hypersensitivity activity of novel non-hallucinogenic compounds derived from iboga alkaloids (i.e., ibogalogs), including tabernanthalog (TBG), ibogainalog (IBG), and ibogaminalog (DM506), using mouse models of neuropathic (Chronic Constriction Injury; CCI) and visceral pain (dextrane sulfate sodium; DSS). Ibogalogs decreased mechanical hyperalgesia and allodynia induced by CCI in a dose- and timeframe-dependent manner, where IBG showed the longest anti-hyperalgesic activity at a comparatively lower dose, whereas DM506 displayed the quickest response. These compounds also decreased hypersensitivity induced by colitis, where DM506 showed the longest activity. To understand the mechanisms involved in these effects, two approaches were utilized: ibogalogs were challenged with the 5-HT2A receptor antagonist ketanserin and the pharmacological activity of these compounds was assessed at the respective 5-HT2A, 5-HT6, and 5-HT7 receptor subtypes. The behavioral results clearly demonstrated that ketanserin abolishes the pain-relieving activity of ibogalogs without inducing any effect per se, supporting the concept that 5-HT2A receptor activation, but not inhibition, is involved in this process. The functional results showed that ibogalogs potently activate the 5-HT2A and 5-HT6 receptor subtypes, whereas they behave as inverse agonists (except TBG) at the 5-HT7 receptor. Considering previous studies showing that 5-HT6 receptor inhibition, but not activation, and 5-HT7 receptor activation, but not inhibition, relieved chronic pain, we can discard these two receptor subtypes as participating in the pain-relieving activity of ibogalogs. The potential involvement of 5-HT2B/2 C receptor subtypes was also ruled out. In conclusion, the anti-hypersensitivity activity of ibogalogs in mice is mediated by a mechanism involving 5-HT2A receptor activation.
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 7
- IUPHAR Article: Psilocybin induces long-lasting effects via 5-HT2A receptors in mouse models of chronic pain. Pharmacological Research May 1, 2025
- Classic Psychedelics in Pain Modulation: Mechanisms, Clinical Evidence, and Future Perspectives ACS Chemical Neuroscience June 6, 2025
- Ibogalogs improve spatial and recognition memory in rodents through a mechanism involving 5-HT2A receptor activation-enhanced NMDA receptor activity in hippocampal pyramidal CA1 neurons Biomedicine & Pharmacotherapy November 13, 2025
- Tabernanthalog, a Non-Hallucinogenic Psychedelic, Alleviates Cancer-Induced Cognitive Deficits via Serotonergic Pathways International Journal of Molecular Sciences August 4, 2025
- Psychoplastogens to Reduce Persistent Cognitive Symptoms for Traumatic Brain Injury as a Chronic Condition Journal of Neurotrauma October 19, 2026
and 2 more in the library
Cites 6
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature 2021
- An analog of psychedelics restores functional neural circuits disrupted by unpredictable stress Molecular Psychiatry May 25, 2021
- Effects of the 5-HT2A receptor antagonist volinanserin on head-twitch response and intracranial self-stimulation depression induced by different structural classes of psychedelics in rodents. Psychopharmacology June 1, 2022
- Tabernanthalog Reduces Motivation for Heroin and Alcohol in a Polydrug Use Model. Psychedelic Medicine June 1, 2023
and 1 more in the library