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Effects of 1-methyl-4-phenylpyridinium on radioligand binding to the NMDA receptor complex
1Dept. of Clinical Neuroscience and Family Medicine, Karolinska Institutet, Huddinge, Sweden.
Abstract:
The present study was performed to determine if 1-methyl-4-phenylpyridinium (MPP+) affects binding of [3H](-)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne maleate ([3H]MK-801), [3H]glutamate and [3H]glycine to the rat and monkey striatal N-methyl-D-aspartate (NMDA) receptor. We found that MPP+ non-competitively inhibits [3H]MK-801 binding with IC50 values between 80 and 330 microM depending on the species and the concentration of glutamate and glycine. MPP+ also partially inhibited [3H]glycine binding without affecting [3H]glutamate binding. We conclude that MPP+ is not an agonist at the NMDA receptor but at high concentrations inhibits NMDA receptor function.