N-methyl-D-aspartate antagonists and drug discrimination

Excitatory amino acids (EAA), such as glutamate, are thought to be involved in various disorders (e.g., ischemic brain damage, epilepsy, Parkinson's d isease), and EAA antagonists have been suggested as potential treatments fo r these disorders. Phencyclidine (PCP), with produces psychotomimetic effec ts in humans, has antagonist properties at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors that have been suggested to underlie some of its actions. This suggestion, and concern about possible psychotomimetic a ctivity, has stimulated research aimed at examining to what extent the beha vioral profile of other NMDA antagonists resembles that of PCP. Drug discri mination (DD) is prominent among the procedures used to carry out such comp arisons. The results of clinical studies with NMDA antagonists provide feed back about the predictive validity of the DD procedures used to characteriz e their preclinical behavioral profile. Further, DD is used also to examine the ability of compounds to attenuate the discriminative stimulus (DS) eff ects of PCP-type drugs, and results of such studies have been suggested to provide evidence of antipsychotic potential. Finally, although many instanc es of intermediate responding in DD can be explained by low efficacy at the receptors that mediate the DS effects of the training drug, certain outcom es produced by PCP-type drugs do not offer valid measures of efficacy, and require more detailed behavioral analyzes. (C) 1999 Elsevier Science Inc.