NMDA Antagonist Properties of the Putative Antiaddictive Drug, Ibogaine. Popik, P., Layer, R.T., Fossom, L.H., et al. J Pharmacol Exp Ther 275:753-760, 1995.
Abstract: Both
anecdotal reports in humans and preclinical studies indicate that
ibogaine interrupts addiction to a variety of abused substances
including alcohol, opiates, 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-i, 2.3 mu M at -60 mV). Consistent
with this observation, ibogaine competitively inhibits [H-3]1-[1-(2-
thienyl)-cyclohexyl]piperidine binding to rat forebrain homogenates
(K-i, 1.5 mu M) and blocks glutamate-induced cell death in neuronal
cultures (IC50, 4.5 mu M). Moreover, at doses previously reported
to interfere with drug-seeking behaviors, ibogaine substitutes
as a discriminative stimulus (ED(50), 64.9 mg/kg) in mice trained
to discriminate the prototypic voltage- dependent NMDA antagonist,
dizocilpine (0.17 mg/kg), from saline. Consistent with previous
reports, ibogaine reduced naloxone- precipitated jumping in morphine-dependent
mice (ED(50), 72 mg/kg). Although pretreatment with glycine did
not affect naloxone-precipitated jumping in morphine-dependent
mice, it abolished the ability of ibogaine to block naloxone-
precipitated jumping. Taken together, these findings link the
NMDA antagonist actions of ibogaine to a putative ''antiaddictive''
property of this alkaloid, its ability to reduce the expression
of morphine dependence
© 1997The Ibogaine Dossier