Effect of agmatine on heteromeric N-methyl-D-aspartate receptor channels

Neurosci Res. 2005 Aug;52(4):387-92. doi: 10.1016/j.neures.2005.05.002.


Endogenous polyamines like spermine are known to have four distinct effects on recombinant N-methyl-d-aspartate (NMDA) receptor channels: voltage-dependent inhibition, glycine-dependent stimulation, glycine-independent stimulation and decreased affinity to the agonist (l-glutamate). These effects are highly dependent on the constituting epsilon subunits (epsilon1-epsilon4) of the recombinant NMDA receptor channels. Agmatine reportedly inhibits native NMDA receptor channels in cultured hippocampal neurons. In the present investigation, the effects of agmatine on the epsilon/zeta heteromeric NMDA receptor channels expressed in Xenopus laevis oocytes were examined using the two-electrode voltage clamp method. Agmatine inhibited the four epsilon/zeta (epsilon1/zeta1, epsilon2/zeta1, epsilon3/zeta1 and epsilon4/zeta1) channels with similar sensitivity (an IC50 value of about 300microM at -70mV). This effect was dependent on the membrane potential and was more pronounced at hyperpolarized membrane potentials (voltage-dependent inhibition). Agmatine did not exhibit other stimulatory (glycine-dependent and -independent effects) or inhibitory (decreased affinity to l-glutamate) effects. These properties are similar to the pharmacological profile of well-characterized NMDA receptor channel blockers like phencyclidine and ketamine. Thus, regarding the effects on the NMDA receptor channels, agmatine is not like other endogenous polyamines rather it acts as a channel blocker.

Publication types

  • Comparative Study

MeSH terms

  • Agmatine / pharmacology*
  • Aldehydes / pharmacology
  • Animals
  • Cloning, Molecular
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Drug Interactions
  • Electric Stimulation / methods
  • Epoxy Compounds / pharmacology
  • Glutamic Acid / pharmacology
  • Inhibitory Concentration 50
  • Membrane Potentials / drug effects*
  • Membrane Potentials / genetics
  • Membrane Potentials / physiology
  • Microinjections / methods
  • Oocytes / drug effects
  • Oocytes / physiology
  • Patch-Clamp Techniques / methods
  • Receptors, N-Methyl-D-Aspartate / chemistry*
  • Receptors, N-Methyl-D-Aspartate / drug effects*
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Recombinant Proteins / drug effects
  • Xenopus laevis


  • Aldehydes
  • Epoxy Compounds
  • Receptors, N-Methyl-D-Aspartate
  • Recombinant Proteins
  • Glutamic Acid
  • Agmatine
  • glycinaldehyde