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.
Annals of the New York Academy of Sciences
September 1, 2000
M H Baumann, J P Pablo, S F Ali et al.
37 citations
Ibogaine, a plant-derived alkaloid being studied for substance use disorders, is rapidly converted in the body to its metabolite noribogaine. In rats, noribogaine reaches higher blood levels than ibogaine and persists for at least 24 hours. Noribogaine did not cause tremors or forepaw treading, unlike ibogaine, but both drugs elevated stress hormones corticosterone and prolactin, with ibogaine more potent for corticosterone. Neither drug affected dopamine levels in the nucleus accumbens, but both increased serotonin levels, with noribogaine more potent. Noribogaine is biologically active and likely contributes to ibogaine's effects but may be safer, producing fewer adverse effects like tremors and stress-axis activation.
Neuroreport
January 5, 1998
J P Pablo, D C Mash
27 citations
Noribogaine, a metabolite produced in the body from the natural compound ibogaine, acts as a full agonist at the mu-opioid receptor. In rat thalamic membranes, noribogaine stimulated a 170% increase above basal G-protein activation at sub-micromolar concentrations, an effect blocked by naloxone, confirming opioid receptor involvement. Its intrinsic activity matched that of the full agonists DAMGO and morphine. Ibogaine itself had no significant effect. This full mu-opioid agonist efficacy may explain ibogaine's ability to block acute opiate withdrawal and reduce morphine self-administration.