Life sciences
January 1, 1995
D C Mash, J K Staley, M H Baumann et al.
108 citations
Ibogaine, a hallucinogenic indole, is thought to help treat cocaine, stimulant, and opiate abuse, possibly through a long-acting metabolite. This study reports that 12-hydroxyibogamine, a primary metabolite of ibogaine, binds with high affinity to the serotonin (5-HT) transporter and increases extracellular 5-HT levels. In binding assays, 12-hydroxyibogamine was 50-fold more potent at the 5-HT transporter than at the dopamine transporter, while ibogaine and the metabolite were equally potent at the dopamine transporter. Microdialysis showed that 12-hydroxyibogamine dose-dependently elevated extracellular 5-HT, but neither ibogaine nor its metabolite raised dopamine levels in the nucleus accumbens. The metabolite's enhancement of 5-HT transmission may improve mood and reduce drug craving, potentially explaining ibogaine's ability to interrupt drug-seeking behavior.
Psychopharmacology
September 1, 1996
J K Staley, Q Ouyang, J Pablo et al.
82 citations
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.
Neuroscience letters
June 2, 1995
D C Mash, J K Staley, J P Pablo et al.
82 citations
Ibogaine and its metabolite 12-hydroxyibogamine act at the MK-801 binding site within the NMDA-receptor cation channel. Both compounds competitively displaced [3H]MK-801 binding to membranes from human caudate, cerebellum, and frog spinal cord. Ibogaine was 4-6 times more potent than its metabolite, but both were 50-1000 times less potent than MK-801. Ibogaine (100 µM) and 12-hydroxyibogamine (1 mM) blocked NMDA-induced depolarizations in frog motoneurons by 85-90%. The block was use-dependent and resembled that of MK-801. These findings suggest that ibogaine's ability to interrupt drug-seeking behavior may partly result from its action at the MK-801 binding site.