Ibogaine, a noncompetitive inhibitor of serotonin transport, acts by stabilizing the cytoplasm-facing state of the transporter.
Miriam T Jacobs, Yuan-Wei Zhang, Scott D Campbell, Gary Rudnick
The Journal of biological chemistry October 5, 2007 DOI: 10.1074/jbc.m704456200 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Laboratory study Peer reviewed |
|---|---|
| Population | In vitro (SERT) |
| Intervention | Ibogaine |
| Topics | Ibogaine Serotonin |
| Keywords | Psychoactive compound Anti-addiction drug Brain chemistry Neurobiology Psychopharmacology Addiction treatment Substance abuse therapy Drug rehabilitation Dependency treatment Neurotransmitter Mood chemical |
| Citations | 149 |
| Key points | Ibogaine inhibits serotonin transporter noncompetitively by decreasing transport rate and stabilizes the transporter state from which serotonin dissociates to the cytoplasm, contrasting with cocaine's mechanism. |
Abstract
Ibogaine, a hallucinogenic alkaloid with purported anti-addiction properties, inhibited serotonin transporter (SERT) noncompetitively by decreasing V(max) with little change in the K(m) for serotonin (5-HT). Ibogaine also inhibited binding to SERT of the cocaine analog 2beta-2-carbomethoxy-3-(4-[(125)I]iodophenyl)tropane. However, inhibition of binding was competitive, increasing the apparent K(D) without much change in B(max). Ibogaine increased the reactivity of cysteine residues positioned in the proposed cytoplasmic permeation pathway of SERT but not at nearby positions out of that pathway. In contrast, cysteines placed at positions in the extracellular permeation pathway reacted at slower rates in the presence of ibogaine. These results are consistent with the proposal that ibogaine binds to and stabilizes the state of SERT from which 5-HT dissociates to the cytoplasm, in contrast with cocaine, which stabilizes the state that binds extracellular 5-HT.