Phencyclidine analogues inhibit NMDA-stimulated [3H]GABA release from cultured cortex neurons

The inhibition of [3H]TCP binding to rat cortical membranes by substances of the PCP/sigma-opiate type was compared with effects of the same compounds on N-methyl-D-aspartate (NMDA) responses in cultured mouse cortex neurons. A new technique of excitatory amino acid-induced [3H]GABA (gamma-amino-butyric acid) release in a continuous superfusion model was used for the purpose. A similar rank order of potencies was found for the substances whether as inhibitors of [3H]TCP binding (MK 801 greater than PCP greater than ketamine-cyclazocine) or as antagonists of NMDA (20 microM)-stimulated [3H]GABA release in the cultured neurons (phencyclidine = MK 801 greater than ketamine greater than cyclazocine).