18-Methoxycoronaridine (18-MC) and ibogaine: comparison of antiaddictive efficacy, toxicity, and mechanisms of action.
Stanley D Glick, Isabelle M Maisonneuve, Karen K. Szumlinski
Annals of the New York Academy of Sciences September 1, 2000 DOI: 10.1111/j.1749-6632.2000.tb05211.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | 18-MC ibogaine |
| Dose | 40 mg/kg |
| Topics | Ibogaine |
| Keywords | Addiction treatment Drug discovery Pharmacology research Safer therapeutics |
| Citations | 89 |
| Key points | 18-MC reduces self-administration of multiple drugs of abuse in rats without the toxic effects of ibogaine, suggesting a higher therapeutic index. |
Abstract
18-MC, a novel iboga alkaloid congener, is being developed as a potential treatment for multiple forms of drug abuse. 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 nondrug reinforcer (water). Both ibogaine and 18-MC ameliorate opioid withdrawal signs. Both ibogaine and 18-MC decrease extracellular levels of dopamine in the nucleus accumbens, but only ibogaine increases extracellular levels of serotonin in the nucleus accumbens. Both ibogaine and 18-MC block morphine-induced and nicotine-induced dopamine release in the nucleus accumbens; only ibogaine enhances cocaine-induced increases in accumbal dopamine. Both ibogaine and 18-MC enhance the locomotor and/or stereotypic effects of stimulants. Ibogaine attenuates, but 18-MC potentiates, the acute locomotor effects of morphine; both compounds attenuate morphine-induced locomotion in morphine-experienced rats. Ibogaine produces whole body tremors and, at high doses (> or = 100 mg/kg), cerebellar damage; 18-MC does not produce these effects. Ibogaine, but not 18-MC, decreases heart rate at high doses. While 18-MC and ibogaine have similar affinities for kappa opioid and possibly nicotinic receptors, 18-MC has much lower affinities than ibogaine for NMDA and sigma-2 receptors, sodium channels, and the 5-HT transporter. Both 18-MC and ibogaine are sequestered in fat and, like ibogaine, 18-MC probably has an active metabolite. The data suggest that 18-MC has a narrower spectrum of actions and will have a substantially greater therapeutic index than ibogaine.
Comparable studies
Other preclinical and animal studies on ibogaine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Noncompetitive Functional Inhibition at Diverse, Human Nicotinic Acetylcholine Receptor Subtypes by Bupropion, Phencyclidine, and Ibogaine TE671/RD cells (human muscle-type nAChR) and SH-SY5Y neuroblastoma cells (human... | 1999 | In vitro study | |
| Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Ibogaine- or harmaline-treated rats | 1993 | Experimental animal study | |
| Effects and aftereffects of ibogaine on morphine self-administration in rats. Rats | 1991 | Preclinical experimental study | |
| Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum. Rats | 1994 | Experimental study | |
| Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption Rats | 2005 | Experimental study |
Citations in the library
Cited by 49
- Ketamine psychotherapy for heroin addiction: immediate effects and two-year follow-up. Journal of Substance Abuse Treatment December 1, 2002
- The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation Molecules January 29, 2015
- Antagonism of alpha 3 beta 4 nicotinic receptors as a strategy to reduce opioid and stimulant self-administration. European Journal of Pharmacology March 1, 2002
- Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes. Frontiers in Pharmacology 2018
- Anti-addictive actions of an iboga alkaloid congener: a novel mechanism for a novel treatment. Pharmacology, Biochemistry, and Behavior June 1, 2003
and 44 more in the library
Cites 37
- Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Neuroscience July 1, 1993
- Effects and aftereffects of ibogaine on morphine self-administration in rats. European Journal of Pharmacology April 3, 1991
- Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum. Brain Research September 19, 1994
- Inhibitory effects of ibogaine on cocaine self-administration in rats. European Journal of Pharmacology September 14, 1993
- A preliminary investigation of ibogaine: case reports and recommendations for further study. Journal of Substance Abuse Treatment 1994
and 32 more in the library