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.
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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
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P. Popik is a Fogarty Visiting Fellow on leave from Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
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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
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DOI: https://doi.org/10.1007/BF02245000