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.
Journal of analytical toxicology
October 1, 1995
W L Hearn, J Pablo, G W Hime et al.
44 citations
A sensitive method was developed to measure ibogaine and its major metabolite, 12-hydroxy-ibogamine (noribogaine), in biological fluids and brain tissue. The metabolite was identified using gas chromatography-mass spectrometry. The procedure involves solvent extraction, derivatization with ethyl iodide, and cleanup before analysis. Detection limits were 5 ng/mL for both compounds, and quantitation limits ranged from 5 to 10 ng/mL across all tested matrices. Calibration curves were linear from 3 to 1000 ng/mL or ng/g.