NMDA antagonist properties of the putative antiaddictive drug, ibogaine.
Journal of Pharmacology and Experimental Therapeutics November 1, 1995 Piotr Popik, Richard T. Layer, Linda H. Fossom et al. 100 citations
Ibogaine blocks NMDA receptors in a voltage-dependent manner, with a Ki of 2.3 µM at -60 mV in hippocampal cultures, and competitively inhibits [3H]TCP binding to rat forebrain homogenates (Ki, 1.5 µM). It also blocks glutamate-induced cell death in neuronal cultures (IC50, 4.5 µM). At doses that interfere with drug-seeking behaviors, ibogaine substitutes as a discriminative stimulus (ED50, 64.9 mg/kg) in mice trained to discriminate dizocilpine from saline. Ibogaine reduces naloxone-precipitated jumping in morphine-dependent mice (ED50, 72 mg/kg), an effect abolished by glycine pretreatment. These findings link ibogaine's NMDA antagonist actions to its ability to reduce morphine dependence.