Properties of ibogaine and its principal metabolite (12-hydroxyibogamine) at the MK-801 binding site of the NMDA receptor complex.
D C Mash, J K Staley, J P Pablo, A M Holohean, J C Hackman, R A Davidoff
Neuroscience letters June 2, 1995 DOI: 10.1016/0304-3940(95)11608-y via PubMed
Summary
AI-generated from the abstractIbogaine and its metabolite 12-hydroxyibogamine act at the MK-801 binding site within the NMDA-receptor cation channel. Both compounds competitively displaced [3H]MK-801 binding to membranes from human caudate, cerebellum, and frog spinal cord. Ibogaine was 4-6 times more potent than its metabolite, but both were 50-1000 times less potent than MK-801. Ibogaine (100 µM) and 12-hydroxyibogamine (1 mM) blocked NMDA-induced depolarizations in frog motoneurons by 85-90%. The block was use-dependent and resembled that of MK-801. These findings suggest that ibogaine's ability to interrupt drug-seeking behavior may partly result from its action at the MK-801 binding site.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Postmortem human caudate and cerebellum, frog spinal cord |
| Interventions | Ibogaine 12-hydroxyibogamine |
| Dose | 100 microM ibogaine, 1 mM 12-hydroxyibogamine |
| Citations | 82 |
| Key finding | Ibogaine and 12-hydroxyibogamine competitively bind to the MK-801 site in the NMDA-receptor channel and block NMDA-induced depolarizations in frog motoneurons. |
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.