Properties of ibogaine and its principal metabolite (12-hydroxyibogamine) at the MK-801 binding site of the NMDA receptor complex.
Neurosci Lett
; 192(1): 53-6, 1995 Jun 02.
Article
em En
| MEDLINE
| ID: mdl-7675310
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Maleato de Dizocilpina
/
Receptores de N-Metil-D-Aspartato
/
Ibogaína
Limite:
Adult
/
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Neurosci Lett
Ano de publicação:
1995
Tipo de documento:
Article
País de afiliação:
Estados Unidos