Properties of ibogaine and its principal metabolite (12-hydroxyibogamine) at the MK-801 binding site of the NMDA receptor complex.
Deborah C. Mash, J K Staley, John Pablo, A M Holohean, J C Hackman, R A Davidoff
Neuroscience Letters June 2, 1995 DOI: 10.1016/0304-3940(95)11608-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Postmortem human caudate and cerebellum, frog spinal cord |
| Interventions | Ibogaine 12-hydroxyibogamine |
| Dose | 100 microM ibogaine, 1 mM 12-hydroxyibogamine |
| Topics | Ibogaine |
| Citations | 82 |
| Key findings | Ibogaine and 12-hydroxyibogamine competitively bind to the MK-801 site in the NMDA-receptor channel and block NMDA-induced depolarizations in frog motoneurons. |
Abstract
The putative anti-addiction alkaloid ibogaine and its principal metabolite 12-hydroxyibogamine appear to act at the (+)-5 methyl-10,11,dihydro-5H- dibenzo[a,d]cycloheten-5-10-imine maleate (MK-801) binding site in the N-methyl-D-aspartate (NMDA)-receptor cation channel. This conclusion is based on findings that both compounds competitively displaced specific [3H]MK-801 binding to membranes from postmortem human caudate and cerebellum and from frog spinal cord. Ibogaine was 4-6-fold more potent than its metabolite and both compounds were less potent (50-1000-fold) than MK-801 binding to the NMDA receptor. In addition, ibogaine (100 microM) and 12-hydroxyibogamine (1 mM) blocked (85-90% of control) the ability of NMDA (100 microM, 5 s) to depolarize frog motoneurons in the isolated frog spinal cord. The prevention of NMDA-depolarizations in frog motoneurons showed use-dependency and was very similar to the block produced by MK-801. In view of the abilities of MK-801 to affect the responses to addictive substances in pre-clinical investigations, our results are compatible with the idea that the ability of ibogaine and 12-hydroxyibogamine to interrupt drug-seeking behavior may, in part, result from their actions at the MK-801 binding site.
Comparable studies
Other experimental studies on ibogaine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ibogaine, a noncompetitive inhibitor of serotonin transport, acts by stabilizing the cytoplasm-facing state of the transporter. In vitro (SERT) | 2007 | Laboratory study | |
| Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies. | 1992 | Laboratory study | |
| The mechanistic basis for noncompetitive ibogaine inhibition of serotonin and dopamine transporters. | 2012 | Experimental study | |
| Identification of a primary metabolite of ibogaine that targets serotonin transporters and elevates serotonin. | 1995 | Experimental study | |
| Ibogaine and its congeners are sigma 2 receptor-selective ligands with moderate affinity. | 1995 | Laboratory study |
Citations in the library
Cited by 57
- Treatment of acute opioid withdrawal with ibogaine. American Journal on Addictions 1999
- 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
- Medication Development of Ibogaine as a Pharmacotherapy for Drug Dependencea. Annals of the New York Academy of Sciences May 1, 1998
- Complementary medicines in psychiatry: review of effectiveness and safety. The British Journal of Psychiatry February 1, 2006
- Mechanisms of Antiaddictive Actions of Ibogainea. Annals of the New York Academy of Sciences May 1, 1998
and 52 more in the library
Cites 9
- 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
- Effects of ibogaine on acute signs of morphine withdrawal in rats: independence from tremor. Neuropharmacology May 1, 1992
- Receptor binding profile suggests multiple mechanisms of action are responsible for ibogaine's putative anti-addictive activity. Psychopharmacology April 1, 1995
and 4 more in the library