Novel iboga alkaloid congeners block nicotinic receptors and reduce drug self-administration.
Christopher J Pace, Stanley D Glick, Isabelle M Maisonneuve, Li-Wen He, Patrick A Jokiel, Martin E. Kuehne, Mark W Fleck
European Journal of Pharmacology May 1, 2004 DOI: 10.1016/j.ejphar.2004.03.062 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical in vitro and animal study Peer reviewed |
|---|---|
| Population | HEK 293 cells expressing recombinant nicotinic alpha3beta4 or NMDA NR1/NR2B receptors, and animal models of morphine and methamphetamine self-administration |
| Intervention | 18-Methoxycoronaridine congeners |
| Measures | IC(50) values at nicotinic alpha3beta4 receptors and NMDA receptors, morphine self-administration, methamphetamine self-administration |
| Topics | Ibogaine |
| Keywords | Cell line Animals Humans Rats, long-evans Tabernaemontana Amphetamine-related disorders Morphine dependence Receptors, n-methyl-d-aspartate Receptors, nicotinic Nicotinic antagonists Self administration Patch-clamp techniques Reward Dose-response relationship, drug Female |
| Key points | Five 18-methoxycoronaridine congeners had inhibitory potencies at nicotinic alpha3beta4 receptors similar to 18-methoxycoronaridine and were ineffective at NMDA receptors; these congeners also reduced morphine and methamphetamine self-administration in animals. The authors argue this supports nicotinic alpha3beta4 receptors as a therapeutic target for drug seeking and that the compounds may constitute a new class of anti-addiction agents. |
Abstract
18-Methoxycoronaridine, a novel iboga alkaloid congener, reduces drug self-administration in animal models of addiction. Previously, we proposed that these effects are mediated by the ability of 18-methoxycoronaridine to inhibit nicotinic alpha3beta4 acetylcholine receptors. In an attempt to identify more potent 18-methoxycoronaridine analogs, we have tested a series of 18-methoxycoronaridine congeners by whole-cell patch clamp recording of HEK 293 cells expressing recombinant nicotinic alpha3beta4 receptors or glutamate NR1/NR2B N-methyl-d-aspartate (NMDA) receptors. The congeners exhibited a range of inhibitory potencies at alpha3beta4 receptors. Five congeners had IC(50) values similar to 18-methoxycoronaridine, and all of these were ineffective at NMDA receptors. The congeners also retained their ability to reduce morphine and methamphetamine self-administration. These data are consistent with the importance of nicotinic alpha3beta4 receptors as a therapeutic target to modulate drug seeking. These compounds may constitute a new class of synthetic agents that act via the nicotinic alpha3beta4 mechanism to combat addiction.
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 25
- Clinical applications of hallucinogens: A review. Experimental and Clinical Psychopharmacology August 1, 2016
- The ibogaine medical subculture. Journal of Ethnopharmacology January 4, 2008
- Fatalities temporally associated with the ingestion of ibogaine. Journal of Forensic Sciences March 1, 2012
- A systematic literature review of clinical trials and therapeutic applications of ibogaine. Journal of Substance Abuse Treatment July 1, 2022
- DARK Classics in Chemical Neuroscience: Ibogaine ACS Chemical Neuroscience September 14, 2018
and 20 more in the library
Cites 15
- Noncompetitive Functional Inhibition at Diverse, Human Nicotinic Acetylcholine Receptor Subtypes by Bupropion, Phencyclidine, and Ibogaine Journal of Pharmacology and Experimental Therapeutics 1999
- A preliminary investigation of ibogaine: case reports and recommendations for further study. Journal of Substance Abuse Treatment 1994
- Attenuation of alcohol intake by ibogaine in three strains of alcohol-preferring rats. Pharmacology, Biochemistry, and Behavior November 1, 1995
- 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
- 18-Methoxycoronaridine, a non-toxic iboga alkaloid congener: effects on morphine and cocaine self-administration and on mesolimbic dopamine release in rats. Brain Research May 6, 1996
and 10 more in the library