Abstract
Ibogaine is a putative anti-addictive drug with potential efficacy for the treatment of opiate, stimulant, and alcohol abuse. We now report ibogaine is a competitive inhibitor (Ki, 1.01±0.1 µM) of [3H]MK-801 binding toN-methyl-D-aspartate (NMDA) receptor coupled cation channels. Since MK-801 can attenuate the development of tolerance to morphine and alcohol as well as sensitization to stimulants in preclinical studies, the reported ability of ibogaine to modify drug-seeking behavior in man may be attributable to a blockade of NMDA receptor coupled cation channels.
This is a preview of subscription content, log in via an institution to check access.
References
Deecher DC, Teitler M, Soderlund DM, Bornmann WG, Kuehne ME, Glick SD (1992) Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies. Brain Res 571:242–247
Dybowsky J, Landrin E (1901) Sur l'Iboga, ses propriétés excitantes, sa composition et sur l'alcaloïde noveau qu'il renferme, l'ibogaïne. C R Acad Sci (Paris) 133:748–750
Glick SD, Rossman K, Steindorf S, Maisonneuve IM, Carlson JN (1991) Effects and aftereffects of ibogaine on morphine self-administration in rats. Eur J Pharmacol 195:341–345
Glick SD, Rossman K, Rao NC, Maisonneuve IM, Carlson JN (1992) Effects of ibogaine on acute signs of morphine withdrawal in rats: independence from tremor. Neuropharmacology 31:497–500
Glick SD, Rossman K, Wang S, Dong N, Keller RW Jr (1993) Local effects of ibogaine on extracellular levels of dopamine and its metabolites in nucleus accumbens and striatum: Interactions with D-amphetamine. Brain Res 628:201–208
Honore T, Davies SN, Drejer J, Fletcher EJ, Jacobsen P, Lodge D, Nielsen FE (1988) Quinoxalinediones: potent competitive non-NMDA glutamate receptor antagonists. Science 241:701–703
Huettner J, Bean B (1988) Block ofN-methyl-D-aspartate-activated current by the anticonvulsant MK-801: selective binding to open channels. Proc Natl Acad Sci USA 85:1307–1311
Karler R, Calder LD, Chaudhry IA, Turkanis SA (1989) Blockade of “reverse tolerance” to cocaine and amphetamine by MK-801. Life Sci 45:599–606
Khanna JM, Kalant H, Shah G, Chau A (1993) Effect of D-cycloserine on rapid tolerance to ethanol. Pharmacol Biochem Behav 45[4]:983–986
Marvizon JC, Lewin AH, Skolnick P (1989) 1-Aminocyclopropan e carboxylic acid: a potent and selective ligand for the glycine modulatory site of theN-methyl-D-aspartate receptor complex. J Neurochem 52:992–994
Pudiak CM, Bozarth MA (1993) L-NAME and MK-801 attenuate sensitization to the locomotor-stimulating effect of cocaine. Life Sci 53[20]:1517–1524
Schneider JA, Sigg EB (1957) Neuropharmacological studies on ibogaine, an indole alkaloid with central stimulant properties. Ann NY Acad Sci 66:765–766
Schoepp DD, True RA (1992) 1S,3R-ACPD — sensitive (metabotropic) [3H]glutamate receptor binding in membranes. Neurosci Lett 145:100–104
Sershen H, Hashim A, Harsing L, Lajtha A (1992) Ibogaine antagonizes cocaine-induced locomotor stimulation in mice. Life Sci 50:1079–1086
Sershen H, Hashim A, Lajtha A (1994) Ibogaine reduces preference for cocaine consumption in C57BL/6By mice. Pharmacol Biochem Behav 47[1]:13–19
Trujillo KA, Akil H (1991) Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. Science 251:85–87
Wu PH, Michic SJ, Liu J-F, Dzung Le A, Kalant H (1993) Blockade of chronic tolerance to ethanol by the NMDA antagonist, (+)-MK 801. Eur J Pharmacol 231:157–164
Author information
Authors and Affiliations
Additional information
P. Popik is a Fogarty Visiting Fellow on leave from Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Rights and permissions
About this article
Cite this article
Popik, P., Layer, R.T. & Skolnick, P. The putative anti-addictive drug ibogaine is a competitive inhibitor of [3H]MK-801 binding to the NMDA receptor complex. Psychopharmacology 114, 672–674 (1994). https://doi.org/10.1007/BF02245000
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02245000