Long-term desipramine or chlorpromazine treatment and rat brain N-methyl-D-aspartate receptor.

The effects of tricyclic antidepressants and antipsychotic drugs on the NMDA receptor in rat brain were investigated. Both types of drugs, in the micromolar concentration range and with Hill coefficients greater than unity, inhibited the binding of [3H]TCP to rat brain membranes. Tricyclic antidepressants containing secondary amine on the aliphatic side chain were more potent than the corresponding tertiary amine derivatives. Antipsychotic drugs containing large side chains were much less active than chlorpromazine. Neither tricyclic antidepressants nor antipsychotic drugs had an inhibitory effect on [3H]CPP binding to the glutamate site of the NMDA complex. Chronic administration of desipramine or chlorpromazine did not change the binding parameters of [3H]TCP to rat cerebral cortex membranes. It is possible that these psychoactive drugs bind to a site adjacent to the [3H]TCP binding site within the ionic channel of the NMDA receptor complex.