Ibogaine, a noncompetitive inhibitor of serotonin transport, acts by stabilizing the cytoplasm-facing state of the transporter.
The Journal of biological chemistry October 5, 2007 Miriam T Jacobs, Yuan-Wei Zhang, Scott D Campbell et al. 149 citations
Ibogaine, a hallucinogenic alkaloid reported to help treat addiction, inhibits the serotonin transporter (SERT) through a noncompetitive mechanism, reducing the maximum transport rate (Vmax) with little effect on serotonin's binding affinity (Km). It also competitively blocks binding of a cocaine analog to SERT, increasing the apparent dissociation constant (KD) without altering the number of binding sites (Bmax). Ibogaine increases reactivity of cysteine residues in the proposed cytoplasmic permeation pathway of SERT but slows reactivity of cysteines in the extracellular pathway. These findings suggest ibogaine binds to and stabilizes the SERT state from which serotonin dissociates into the cytoplasm, opposite to cocaine's action, which stabilizes the state that binds extracellular serotonin.