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

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 C PZ (at 30-1000 muM) strongly slowed down the deactivation process in a dose -dependent manner. At high CPZ concentration (1 mM), the NMDA-elicited curr ents were insensitive to NMDA removal as long as CPZ was present and deacti vated only when both NMDA and CPZ were washed out. CPZ by itself did not ac tivate any current. These data indicate that one of CPZ actions is to stabi lise the open conformation of NMDA receptors probably by fixing it in the b ound state. This CPZ effect may be important as the synaptic currents repre sent mainly the deactivation process. (C) 2001 Elsevier Science Ireland Ltd . All rights reserved.