The effects of ibogaine on dopamine and serotonin transport in rat brain synaptosomes.
G B Wells, M C Lopez, J C Tanaka
Brain Research Bulletin April 1, 1999 DOI: 10.1016/s0361-9230(99)00053-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | Rat brain synaptosomes |
| Intervention | Ibogaine |
| Dose | 20 microM and 50 microM |
| Topics | Serotonin Ibogaine |
| Keywords | Ibogaine natural compound Anti-addictive properties Neurotransmitter regulation dopamine Crucial messengers Blocking reuptake Inhibiting release Modulate brain levels Multiple pathways |
| Citations | 30 |
| Key findings | Ibogaine competitively blocks dopamine and serotonin uptake and inhibits serotonin release, but these effects occur only at micromolar concentrations, indicating involvement of multiple neurotransmitter pathways in its anti-addictive properties. |
Abstract
Ibogaine has been shown to affect biogenic amine levels in selected brain regions. Because of the involvement of these neurotransmitters in drug addiction, the effects of ibogaine on biogenic amine transport may contribute to the potential anti-addictive properties of ibogaine in vivo. With rat brain synaptosomes as our experimental system, we measured the effects of ibogaine on the uptake and release of dopamine (DA) and serotonin (5-HT). Ibogaine competitively blocked both DA and 5-HT uptake with IC50 values of 20 microM at 75 nM 3H-DA and 2.6 microM at 10 nM 3H-5-HT. Ibogaine had no effect on K+-induced release of 3H-DA from preloaded synaptosomes, but 20 microM and 50 microM ibogaine inhibited roughly 40% and 60%, respectively, of the K(+)-induced release of 3H-5-HT from preloaded synaptosomes. In the absence of a depolarizing stimulus, ibogaine evoked a small release of 3H-DA but not 3H-5-HT. These relatively low-potency effects of ibogaine on DA and 5-HT uptake in synaptosomes are consistent with the low binding affinity of ibogaine that has been previously reported for DA and 5-HT transporters. Our results show that if ibogaine modulates DA and 5-HT levels in the brain by directly blocking their uptake, then a concentration of ibogaine in the micromolar range is required. Furthermore, if the anti-addictive effects of ibogaine require this concentration, then ibogaine likely exerts these effects through a combination of neurotransmitter pathways, because binding affinities and functional potencies of ibogaine in the micromolar range have been reported for a variety of neuronal receptors and transporters.
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 16
- The mechanistic basis for noncompetitive ibogaine inhibition of serotonin and dopamine transporters. Journal of Biological Chemistry May 25, 2012
- Conformational dynamics of the human serotonin transporter during substrate and drug binding. Nature Communications April 11, 2019
- Ibogaine Administration Modifies GDNF and BDNF Expression in Brain Regions Involved in Mesocorticolimbic and Nigral Dopaminergic Circuits. Frontiers in Pharmacology 2019
- In Vivo Neurobiological Effects of Ibogaine and Its O-Desmethyl Metabolite, 12-Hydroxyibogamine (Noribogaine), in Rats Journal of Pharmacology and Experimental Therapeutics May 1, 2001
- The ethnobotany of psychoactive plant use: a phylogenetic perspective PeerJ January 19, 2017
and 11 more in the library
Cites 35
- Effects and aftereffects of ibogaine on morphine self-administration in rats. European Journal of Pharmacology April 3, 1991
- 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
- Ibogaine possesses a selective affinity for sigma 2 receptors. Life Sciences 1995
- Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies. Brain Research February 7, 1992
and 30 more in the library