CEREBROSPINAL-FLUID AND SERUM CONCENTRATIONS OF THE N-METHYL-D-ASPARTATE (NMDA) RECEPTOR ANTAGONIST MEMANTINE IN MAN

Memantine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist with therapeutic potential in dementia, spasticity and Parkinson's disease. The K-i-value of memantine at the phencyclidine (PCP) binding site of the NMDA receptor is 0.5 mu M in human frontal cortex, We investigated whether concentrations of memantine in cerebrospinal fluid (CSF) and serum samples under therapeutic conditions are in the range of its K-i-value at the PCP binding site. The serum levels ranged from 0.025 to 0.529 mu M with daily doses between 5 and 30 mg. CSF levels were highly correlated to serum levels and were below serum levels in each patient with a mean CSF/serum ratio of 0.52. Serum and CSF levels were correlated to the daily dose, but not to the duration of treatment. At the concentrations reported here, memantine is expected to specifically interact with the PCP binding site of the NMDA receptor.