ASSESSING STRUCTURAL-CHANGES IN THE BRAIN TO EVALUATE NEUROTOXICOLOGICAL EFFECTS OF NMDA RECEPTOR ANTAGONISTS

Like all pharmacologic agents known, N-methyl-D-aspartate (NMDA) antag onist compounds have side effects. It is expected that neuroactive mol ecules have effects, including side effects, in the central nervous sy stem (CNS), With NMDA antagonists in rodents, these side effects are r emarkably focal in the cingulate and retrosplenial cortex, The salient features of NMDA antagonist neurotoxicity which should be underscored are hypermetabolism, lactate accumulation, neuronal vacuolization in aldehyde fixed material, and neuronal death in older rodents, The scop e of this phenomenon must urgently be determined in nonrodent species, specifically primates, This is important from both a regulatory and n eurotherapeutic point of view, since effective molecules having potent ial in human disease states may also have NMDA antagonist properties.