PROPERTIES OF IBOGAINE AND ITS PRINCIPAL METABOLITE (12-HYDROXYIBOGAMINE) AT THE MK-801 BINDING-SITE OF THE NMDA RECEPTOR COMPLEX

NEUROSCIENCE LETTERS

卷:192

Article

MASH, DC ; STALEY, JK ; PABLO, JP ; HOLOHEAN, AM ; HACKMAN, JC ; DAVIDOFF, RA

关键词: IBOGAINE;    12-HYDROXYIBOGAMINE;    MK-801;    N-METHYL-D-ASPARTATE RECEPTORS;    SPINAL CORD;    CAUDATE;    CEREBELLUM;    DRUG ABUSE;   

DOI  :  10.1016/0304-3940(95)11608-Y

来源: Elsevier

【 摘 要 】

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 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 [H-3]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 mu M) and 12-hydroxyibogamine (1 mM) blocked (85-90% of control) the ability of NMDA (100 mu M, 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.

【 授权许可】

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