Different sensitivities of NMDA receptor channel subtypes to non-competitive antagonists

Neuroreport. 1993 Jun;4(6):687-90. doi: 10.1097/00001756-199306000-00021.


Four kinds of heteromeric N-methyl-D-aspartate (NMDA) receptor channels, the epsilon 1/zeta 1, epsilon 2/zeta 1, epsilon 3/zeta 1 and epsilon 4/zeta 1 channels, were expressed in Xenopus oocytes and their sensitivities to various non-competitive antagonists were examined. The epsilon 1/zeta 1 and epsilon 2/zeta 1 channels were more sensitive to (+)MK-801 (dizocilpine) than the epsilon 3/zeta 1 and epsilon 4/zeta 1 channels, whereas the sensitivities to phencyclidine (PCP), ketamine and N-allylnormetazocine (SKF-10,047) were only slightly variable among the four epsilon/zeta channels. Furthermore, the replacement by glutamine or arginine of the conserved asparagine residue in segment M2 of the epsilon 2 and zeta 1 NMDA receptor channel subunits reduced the sensitivities to PCP, ketamine and SKF-10,047, though to different extents. These results, together with previous findings, suggest that these non-competitive antagonists as well as (+)MK-801 and Mg2+ act on a common site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Dizocilpine Maleate / pharmacology
  • Ketamine / pharmacology
  • Magnesium / pharmacology
  • Molecular Sequence Data
  • Mutagenesis
  • Oocytes / metabolism
  • Phenazocine / analogs & derivatives
  • Phenazocine / pharmacology
  • Phencyclidine / pharmacology
  • RNA, Messenger / metabolism
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Xenopus


  • RNA, Messenger
  • Receptors, N-Methyl-D-Aspartate
  • Ketamine
  • Dizocilpine Maleate
  • SK&F 10047
  • Magnesium
  • Phenazocine
  • Phencyclidine