Printed in U.S.A. NMDA Antagonist Properties of the Putative Antiaddictive

Both anecdotal reports in humans and preclinical studies mdi-cate that ibogaine interrupts addiction to a variety of abused substances mncludmng alcohol, opmates, nicotine and stimulants. Based on the similarity of these therapeutic claims to recent preclinical studies demonstrating that N-methyl-D-aspartate (NMDA) antagonists attenuate addiction-related phenomena, we examined the NMDA antagonist properties of ibogaine. Pharmacologically relevant concentrations of ibogaine produce a voltage-dependent block of NMDA receptors in hippocampal cultures (K,, 2.3 pM at-60 my). Consistent with this observa-tion, ibogaine competitively inhibits rH]1-[1-(2-thienyl)-cyclo-hexyl]piperidmne binding to rat forebrain homogenates (K,, 1.5 &M) and blocks glutamate-induced cell death in neuronal cul-tures (IC50, 4.5 SM). Moreover, at doses previously reported t