The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist.

  title={The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist.},
  author={E. Wong and J. Kemp and T. Priestley and A. R. Knight and G. Woodruff and L. Iversen},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  volume={83 18},
  • E. Wong, J. Kemp, +3 authors L. Iversen
  • Published 1986
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
The compound MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine maleate)] is a potent anticonvulsant that is active after oral administration and whose mechanism of action is unknown. We have detected high-affinity (Kd = 37.2 +/- 2.7 nM) binding sites for [3H]MK-801 in rat brain membranes. These sites are heat-labile, stereoselective, and regionally specific, with the hippocampus showing the highest density of sites, followed by cerebral cortex, corpus striatum, and… Expand
The novel anticonvulsant MK-801: a potent and specific ligand of the brain phencyclidine/gd-receptor
Findings support the concept that the anticonvulsant and anti-NMDA effects of MK-801 result from its being the most potent known ligand of PCP/sigma-receptors. Expand
The novel anticonvulsant MK-801 interacts with central phencyclidine recognition sites in rat brain.
Findings in the present study provide evidence for the possible existence of an N M D A / P C P receptor complex in rat brain via a direct interaction with PCP sites. Expand
The Antidepressant Metapramine is a Low-affinity Antagonist at N-methyl-d-aspartic Acid Receptors
The results suggest that metapramine is a low-affinity antagonist of the NMDA receptor complex channel, which could be useful for the treatment of diseases linked to excessive stimulation of glutamatergic NMDA receptors. Expand
Comparison of the behavioral and biochemical effects of the NMDA receptor antagonists, MK-801 and phencyclidine.
The results suggest that the behavioral responses induced by MK-801 involve primarily the PCP receptor and the dopamine system, and that the differences from PCP reflect a reduced effect on the 5-HT neuronal system. Expand
The interaction between MK-801 and receptors for n-methyl-d-aspartate : Functional consequences
MK-801 was highly effective in preventing loss of hippocampal neurones following bilateral occlusion of the common carotid arteries in the gerbil and caused essentially complete protection against loss of neurones produced by injection of neurotoxic doses of NMDA or quinolinic acid into the striatum or hippocampus. Expand
Effects of NMDA antagonists, MK-801 and CPP, upon local cerebral glucose use
The data indicate that widespread, anatomically organised alterations in cerebral function are associated with the administration of NMDA receptor antagonists despite the minor role normally ascribed to these receptors in conventional fast synaptic transmission. Expand
Harmaline competitively inhibits [ 3H ]MK-801 binding to the NMDA receptor in rabbit brain
In vitro evidence is provided that the competitive blockade of harmaline-induced tremor by MK-801 occurs within the calcium channel coupled to the NMDA receptor. Expand
Sustained antidepressant action of the N-methyl-D-aspartate receptor antagonist MK-801 in a chronic unpredictable mild stress model.
The present study revealed the sustained antidepressant effects of MK-801 in the CUMS model and suggested synaptogenesis and neuronal regeneration in the prelimbic regions of mPFC, DG and CA3 of the hippocampus may be implicated as mechanisms that promote a sustained antidepressant response. Expand
In vivo labelling of the NMDA receptor channel complex by [3H]MK-801.
An in vivo radioligand binding assay for the N-methyl-D-aspartate (NMDA) receptor channel complex in the mouse brain has been developed using the non-competitive NMDA receptor antagonist [3H]MK-801.Expand
[3H]MK-801 binding sites in post-mortem human frontal cortex.
The results demonstrate the presence of binding sites forMK-801 in post-mortem human brains and provide evidence for binding site heterogeneity and add support to the hypothesis that MK-801, glutamate, glycine and magnesium all bind to different sites on the NMDA receptor-ion channel complex. Expand


Nature ( London ) 307 , 460 - 462
  • Proc . Nati . Acad . Sci . USA
  • 1984