Chlorpromazine prolongs the deactivation of N-methyl-D-aspartate-induced currents in cultured rat hippocampal neurons

Neurosci Lett. 2001 Nov 23;315(1-2):1-4. doi: 10.1016/s0304-3940(01)02245-5.

Abstract

The effect of chlorpromazine (CPZ) on deactivation of N-methyl-D-aspartate (NMDA)-induced currents was studied in the whole-cell configuration of the patch-clamp technique in cultured rat hippocampal neurons. We report that CPZ (at 30-1000 microM) strongly slowed down the deactivation process in a dose-dependent manner. At high CPZ concentration (1 mM), the NMDA-elicited currents were insensitive to NMDA removal as long as CPZ was present and deactivated only when both NMDA and CPZ were washed out. CPZ by itself did not activate any current. These data indicate that one of CPZ actions is to stabilise the open conformation of NMDA receptors probably by fixing it in the bound state. This CPZ effect may be important as the synaptic currents represent mainly the deactivation process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Cells, Cultured
  • Chlorpromazine / pharmacology*
  • Excitatory Amino Acid Agonists / pharmacology*
  • Excitatory Postsynaptic Potentials
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • N-Methylaspartate / pharmacology*
  • Neurons / drug effects*
  • Neurons / physiology
  • Patch-Clamp Techniques
  • Rats

Substances

  • Antipsychotic Agents
  • Excitatory Amino Acid Agonists
  • N-Methylaspartate
  • Chlorpromazine