J. Kornhuber, J. Bormann, W. Retz
Aug 3, 1989
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1
Influential Citations
256
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Journal
European journal of pharmacology
Abstract
It has recently been shown that MK-801 ((+ )5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate), a NMDA antagonist, has therapeutic activity in an animal model of Parkinson's disease. MK-801 reversed the reduced locomotor activity in the reserpineand amethyl-paratyrosine-pretreated mouse, indicating a mechanism independent of dopamine or noradrenaline release (Carlsson and Carlsson, 1989). This suggests that NMDA antagonists might be useful in the treatment of Parkinson's disease . Conversely, antiparkinson drugs might have NMDA antagonistic activity (Olney et al ., 1987) . The present investigation demonstrates that the long known antiparkinson and antipastic substance, memantine (1-amino-3,5-dimethyladamantane), inhibits the binding of [ 3H]MK-801 to postmortem human brain homogenates at therapeutic concentrations . Tissue from the frontal cortex was taken at autopsy from 3 subjects with no apparent history of neurological or psychiatric disorders . There were 2 males, aged 36 and 60, and 1 female aged 85 years. The postmortem interval was between 24 and 48 h. All details of the experimental procedures were identical to those previously described (Kornhuber et al., 1989) . MK-801 and memantine were investigated within the same assay and all