The N-methyl-D-aspartate receptor channel blocker amantadine does not cause histopathological alterations in human brain tissue

Low doses of N-methyl-D-aspartate (NMDA)-type glutamate receptor antagonist s induce morphological alterations in neurons of the cingulate gyrus and re trosplenial cortex of the rat. Neuronal cell death may result at higher dos es. These effects are a major concern with regard to the introduction of ne w NMDA receptor antagonists into clinical trials. Amantadine is an uncompet itive NMDA receptor antagonist, which has been in clinical use for many yea rs. In the present study we have looked for possible morphological alterati ons like necrosis in postmortem human brain tissue of patients previously t reated with amantadine. Formalin-fixed tissue samples were taken from the h ippocampus, cingulate gyrus, and retrosplenial cortex of 8 patients on prev ious amantadine medication and of 11 controls. Histopathological examinatio n of sections was performed blind. All brains except one revealed either no nspecific age-related or cerebrovascular changes or other neurodegrenerativ e disorders including Alzheimer's, Parkinson's or Lewy body disease. In con clusion, histopathological examination of the hippocampus, retrosplenial co rtex, and cingulate gyrus of human brain did not reveal changes suggested t o be specific for previous amantadine treatment.