Differential effects of chlorpromazine on ionotropic glutamate receptors in cultured rat hippocampal neurons

The effect of a widely used phenothiazine, chlorpromazine (CPZ) on ionotropic glutamate receptors was investigated using the patch-clamp technique in cultured rat hippocampal neurons. The non-N-methyl-D-aspartate (NMDA) receptors were insensitive to CPZ. The current responses to NMDA showed a wide range of variability of both the rate and the extent of desensitization. The responses characterized by fast and profound desensitization were strongly inhibited by 30 muM CPZ. The effectiveness of block of NMDA responses was clearly correlated with the apparent time constant of the desensitization onset. The extent of desenstitization was found to be increased by CPZ. We conclude that CPZ inhibits the NM DA receptors and propose that the sensibility to CPZ may depend both on the subunit composition and on the state of receptor modulation by intracellular factors. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.