Ibogaine, one of several
alkaloids found in the root bark of the African shrub Tabernanthe iboga, has been claimed to be effective in treating multiple forms of
drug abuse. Problems associated with side effects of
ibogaine have spawned a search for more effective and safer structural derivatives.
18-Methoxycoronaridine (18-MC), a novel iboga
alkaloid congener, appears to have substantial potential for broad use as an anti-addictive
therapy. Like
ibogaine (40 mg/kg), 18-MC (40 mg/kg) decreases the intravenous
self-administration of
morphine and
cocaine and the oral
self-administration of
ethanol and
nicotine in rats; unlike
ibogaine, 18-MC does not affect responding for a non-
drug reinforcer (water).
Ibogaine and 18-MC appear to reduce the reinforcing efficacies, rather than the potencies, of drugs of abuse. Both
ibogaine and 18-MC decreases extracellular levels of
dopamine in the nucleus accumbens while only
ibogaine increases
serotonin levels in this brain region. Both
ibogaine and 18-MC block
morphine-induced and
nicotine-induced
dopamine release in the accumbens; only
ibogaine enhances
cocaine-induced increases in
dopamine levels.
Ibogaine produces whole body
tremors and, at high doses (at least 100 mg/kg), cerebellar damage; 18-MC does not produce these effects.
Ibogaine, but not 18-MC, causes
bradycardia at high doses.
Ibogaine and its metabolite
noribogaine have low microM affinities for kappa and
mu opioid receptors,
NMDA receptors, 5HT-3 receptors, sigma-2 sites,
sodium channels and the
serotonin transporter. 18-MC has low microM affinities at all three
opioid receptors and at 5HT-3 receptors but much lower or no affinities for
NMDA and
sigma-2 receptors,
sodium channels, and the
5HT transporter. Both 18-MC and
ibogaine are sequestered in fat and, like
ibogaine, 18-MC probably has an active metabolite. 18-MC also has (+) and (-) enantiomers, both of which are active. Considered together, all of the data indicate that 18-MC should be safer than
ibogaine and at least as efficacious as an anti-addictive medication.