MK-801 inhibition of nicotinic acetylcholine receptor channels

Synapse. 1991 Mar;7(3):207-15. doi: 10.1002/syn.890070305.


MK-801 is a potent inhibitor of the NMDA subtype of glutamate receptors. Single-channel and macroscopic currents indicate that MK-801 also inhibits nicotinic acetylcholine receptors (nAChRs). MK-801 does not significantly increase desensitization of the nAChRs or compete for the ACh binding site. Although there is a slight inhibition of the closed nAChR, the main action of MK-801 is to enter and block the open channel. The voltage dependence for block is consistent with a single binding site within the channel that is 50% of the way through the membrane field. The IC50 for block is 3 microM at -70 mV for currents induced by 0.5 microM ACh. The data from both single-channel and macroscopic currents can be used to estimate a Kd (0) of 7 microM, which is about 40 times higher than the Kd (0) for MK-801 binding to the NMDA receptor. The relative potency of tricyclic compounds like MK-801 for various neurotransmitter systems points out that the pharmacologic action of these drugs could involve complicated interactions in vivo.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Cell Line
  • Dizocilpine Maleate / pharmacology*
  • Dose-Response Relationship, Drug
  • Ion Channel Gating / drug effects
  • Ion Channels / drug effects
  • Ion Channels / physiology*
  • Membrane Potentials / drug effects
  • Mice
  • Muscles
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Receptors, Nicotinic / drug effects
  • Receptors, Nicotinic / physiology*


  • Ion Channels
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Nicotinic
  • Dizocilpine Maleate
  • Acetylcholine