Ibogaine, a treatment for drug dependence, is metabolized into 12-hydroxyibogamine (12-OH ibogamine). Both the parent drug and metabolite bind to similar molecular targets, with the highest potency at the cocaine recognition site on the serotonin transporter. The metabolite shows higher affinity at the kappa-1 receptor and lower affinity at the NMDA receptor compared to ibogaine. Micromolar concentrations of both compounds are found in rat brain. The combined actions of ibogaine and its metabolite at key pharmacological targets may alter drug-seeking behavior by modulating reward circuits.
Five new compounds derived from a fragment of ibogaine were synthesized and tested for their ability to bind to brain receptors and transporters. All five showed 8 to 10 times stronger binding to the dopamine transporter than ibogaine itself. Two compounds were more potent than ibogaine at the serotonin transporter, while the others were weaker. The compounds generally had weak binding to dopamine D1 and D2 receptors, but two showed moderate binding to dopamine D3 receptors. All had weak binding to opioid receptors and NMDA receptors. These derivatives may serve as useful substitutes for ibogaine in addiction therapy.