European journal of pharmacology
March 1, 2002
Stanley D Glick, Isabelle M Maisonneuve, Barbara A Kitchen et al.
120 citations
Ibogaine and a related compound, 18-methoxycoronaridine, block alpha 3 beta 4 nicotinic receptors in the brain, with 18-methoxycoronaridine being more selective for these receptors than ibogaine. Low doses of combinations of 18-methoxycoronaridine with mecamylamine or dextromethorphan, or mecamylamine with dextromethorphan, reduced morphine and methamphetamine self-administration in studies, even though each drug alone at those doses was ineffective. The findings suggest that blocking alpha 3 beta 4 receptors may help reduce drug-seeking behavior, and 18-methoxycoronaridine may represent a new class of anti-addiction agents.
Annals of the New York Academy of Sciences
May 1, 1998
Stanley D Glick, Isabelle M Maisonneuve
93 citations
Ibogaine, an alkaloid from Tabemanthe iboga, can decrease morphine and cocaine self-administration for several days in some rats, with shorter-lasting effects on ethanol and nicotine intake. Both ibogaine and its metabolite noribogaine acutely lower dopamine levels in the nucleus accumbens. Ibogaine pretreatment blocks morphine-induced dopamine release and hyperactivity but enhances similar effects of stimulants like cocaine and amphetamine. The compound binds to kappa opioid, NMDA, serotonin, sigma-2, and nicotinic receptors. Kappa agonist and NMDA antagonist actions appear to contribute to ibogaine's effects on opioid and stimulant self-administration, while serotonergic actions may be more important for reducing alcohol intake. Nicotinic antagonist action may mediate reduced nicotine preferences, and sigma-2 action appears to mediate neurotoxicity.
Addiction biology
October 1, 2010
Sebastien Carnicella, Dao-Yao He, Quinn V Yowell et al.
49 citations
Noribogaine, a metabolite of ibogaine, increases GDNF expression in cell cultures and reduces alcohol self-administration when infused into the ventral tegmental area (VTA) of rats, whereas 18-MC, a synthetic ibogaine derivative, does not affect GDNF expression or alcohol responding in the VTA. These findings indicate that noribogaine and 18-MC act through different mechanisms and brain sites to reduce alcohol consumption, and that noribogaine may share ibogaine's anti-addictive properties without some of its side effects.
European journal of pharmacology
November 21, 2005
Vishal Panchal, Olga D Taraschenko, Isabelle M Maisonneuve et al.
30 citations
18-Methoxyroconaridine (18-MC), a synthetic derivative of ibogaine, reduces morphine self-administration and alleviates several signs of acute opioid withdrawal in rats. The mechanism behind 18-MC's attenuation of opioid withdrawal was unknown. In vitro studies show 18-MC is a potent antagonist of alpha3beta4 nicotinic receptors, predominantly located in the medial habenula and interpeduncular nuclei. To test whether brain areas with high densities of these receptors are involved, 18-MC was locally administered into the medial habenula, interpeduncular nucleus, and locus coeruleus of morphine-dependent rats, followed by naltrexone to precipitate withdrawal.
Drug metabolism and disposition: the biological fate of chemicals
June 1, 2002
Wenjiang Zhang, Yamini Ramamoorthy, Rachel F Tyndale et al.
17 citations
The ibogaine analog 18-methoxycoronaridine (18-MC) is metabolized primarily into 18-hydroxycoronaridine (18-HC) in human liver microsomes. This conversion is mainly catalyzed by the polymorphic enzyme CYP2C19, with a Michaelis constant (K_m) of 1.34 μM and maximum velocity (V_max) of 0.21 nmol/mg/min. Selective inhibition of CYP2C19 reduced 18-HC formation by 65%, and antibodies against CYP2C enzymes inhibited it by 70%. Other cytochrome P450 enzymes showed negligible involvement. The correlation between 18-MC metabolism and S-mephenytoin 4'-hydroxylase activity across five human liver samples further supports CYP2C19's primary role. These results suggest 18-MC could serve as a probe for CYP2C19 activity.