Assessing structural changes in the brain to evaluate neurotoxicological effects of NMDA receptor antagonists

Like all pharmacologic agents known, N-methyl-D-aspartate (NMDA) antagonist compounds have side effects. It is expected that neuroactive molecules have effects, including side effects, in the central nervous system (CNS). With NMDA antagonists in rodents, these side effects are remarkably 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 scope of this phenomenon must urgently be determined in non-rodent species, specifically primates. This is important from both a regulatory and neurotherapeutic point of view, since effective molecules having potential in human disease states may also have NMDA antagonist properties.