Dextromethorphan blocks N-methyl-D-aspartate-induced currents and voltage-operated inward currents in cultured cortical neurons

Eur J Pharmacol. 1993 Jul 20;238(2-3):209-16. doi: 10.1016/0014-2999(93)90849-d.


The effect of dextromethorphan on several types of cation currents in cultured rat cortical neurons and PC12 cells was studied by using the whole-cell configuration of the patch-clamp technique. The Ba2+ current through L- and N-type Ca2+ channels was blocked with similar potencies (52-71 microM) in both types of cells. The effect was not voltage-dependent, in contrast to that of amlodipine (a dihydropyridine). Dextromethorphan was able to block the Ba2+ current completely unlike amlodipine and omega-conotoxin (an N-type channel blocker) which produced only partial inhibition. The voltage-activated Na+ and Ca2+ channels in cortical neurons were inhibited by similar concentrations of dextromethorphan (IC50 approximately 80 microM). The morphinan was at least 100 times more potent (IC50 = 0.55 microM) as a blocker of the current induced by N-methyl-D-aspartate (NMDA) in cortical neurons. Currents induced by (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ((RS)-AMPA) or kainic acid were not significantly affected even at 1 mM. The results suggest that the neuroprotective effect of dextromethorphan, previously found to occur in a concentration range of 10-100 microM, may be due to a complete blockade of the NMDA receptor channel and a partial inhibition of voltage-dependent Ca2+ and Na+ channels.

Publication types

  • Comparative Study

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Amlodipine / pharmacology
  • Animals
  • Barium / metabolism
  • Calcium Channels / drug effects*
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects*
  • Dextromethorphan / pharmacology*
  • Electrophysiology
  • Female
  • Kainic Acid / pharmacology
  • N-Methylaspartate / antagonists & inhibitors
  • Neurons / drug effects*
  • Neurons / metabolism
  • PC12 Cells
  • Rats
  • Receptors, N-Methyl-D-Aspartate / drug effects*
  • Sodium Channels / drug effects*
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology


  • Calcium Channels
  • Receptors, N-Methyl-D-Aspartate
  • Sodium Channels
  • Amlodipine
  • Barium
  • N-Methylaspartate
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Dextromethorphan
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Kainic Acid