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.
Pharmacology, biochemistry, and behavior
June 1, 2003
Isabelle M Maisonneuve, Stanley D Glick
109 citations
18-Methoxycoronaridine (18-MC), a synthetic compound related to iboga, reduces self-administration of multiple addictive drugs in animal models. It decreased intravenous morphine, cocaine, methamphetamine, and nicotine self-administration, as well as oral alcohol and nicotine intake, and eased opioid withdrawal signs, without affecting responding for a nondrug reinforcer (water) or causing apparent toxicity. 18-MC also blocked sensitized dopamine responses to morphine and cocaine in the nucleus accumbens. Receptor studies identified it as a potent antagonist at alpha3beta4 nicotinic receptors. Low-dose combinations of 18-MC with other alpha3beta4 antagonists reduced drug self-administration at otherwise ineffective doses. The findings suggest that alpha3beta4 nicotinic receptor antagonists may offer a novel, broad-spectrum treatment for addiction.
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.
Pharmacology, biochemistry, and behavior
January 1, 2016
Amir H Rezvani, Marty C Cauley, Susan Slade et al.
22 citations
The ibogaine derivative 18-methoxycoronaridine (18-MC), given orally, reduced nicotine and alcohol self-administration in rats. In female rats trained to self-administer nicotine, a single 40 mg/kg oral dose significantly decreased nicotine intake, particularly in animals with lower baseline consumption. In alcohol-preferring rats of both sexes, 18-MC dose-dependently reduced alcohol intake, with all tested doses (10, 20, 40 mg/kg) producing significant reductions. These results indicate that oral 18-MC is effective in curbing both alcohol and nicotine seeking, supporting its potential as a therapy for alcoholism and smoking addiction.
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.
Current Medicinal Chemistry - Central Nervous System Agents
August 1, 2001
Upul K. Bandarage, Martin E. Kuehne, Stanley D Glick
8 citations
Ibogaine, a psychoactive alkaloid from the West African shrub Tabernanthe iboga, can reduce addictive behavior for up to six months after a single oral dose or three years after four treatments in rats, decreasing self-administration of morphine, cocaine, ethanol, and nicotine. However, ibogaine causes serious side effects including tremors, degeneration of Purkinje cells, and acute depression of water-seeking behavior. To overcome these problems, researchers synthesized 18-methoxycoronaridine (18-MC), a novel iboga alkaloid congener, via a 13-step process with 7% yield. In rats, 18-MC similarly reduces self-administration of these drugs but lacks ibogaine's side effects, suggesting potential as a safer treatment for multiple forms of drug abuse.