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.