The putative anti-addictive drug ibogaine is a competitive inhibitor of [3H]MK-801 binding to the NMDA receptor complex.
Ibogaine is a putative anti-addictive drug with potential efficacy for the treatment of opiate, stimulant, and alcohol abuse. We now report ibogaine is a competitive inhibitor (Ki, 1.01 +/- 0.1 microM) of [3H]MK-801 binding to N-methyl-D-aspartate (NMDA) receptor coupled cation channels. Since MK-801 can attenuate the development of tolerance to morphine and alcohol as well as sensitization to stimulants in preclinical studies, the reported ability of ibogaine to modify drug-seeking behavior in man may be attributable to a blockade of NMDA receptor coupled cation channels.
Popik
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Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892-0008.
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Skolnick
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D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D007050:Ibogaine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008024:Ligands; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*
D007473:Ion Channels; D008024:Ligands; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D007050:Ibogaine; D016291:Dizocilpine Maleate; C012058:tenocyclidine; D010622:Phencyclidine