title: Properties of ibogaine and its principal metabolite (12-hydroxyibogamine) at the MK-801 binding site of the NMDA receptor complex.
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.
authors.affiliation: Department of Neurology, University of Miami School of Medicine, FL 33101, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Mash
authors.forename: J K
authors.initials: JK
authors.lastname: Staley
authors.forename: J P
authors.initials: JP
authors.lastname: Pablo
authors.forename: A M
authors.initials: AM
authors.lastname: Holohean
authors.forename: J C
authors.initials: JC
authors.lastname: Hackman
authors.forename: R A
authors.initials: RA
authors.lastname: Davidoff
mesh_terms: D000328:Adult; D000818:Animals; D001667:Binding, Competitive; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007050:Ibogaine / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011894:Rana pipiens; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D007050:Ibogaine; D016291:Dizocilpine Maleate