EFFECTS OF 1-METHYL-4-PHENYLPYRIDINIUM ON RADIOLIGAND BINDING TO THE NMDA RECEPTOR COMPLEX

The present study was performed to determine if 1-methyl-4-phenylpyrid inium (MPP(+)) affects binding of 0,11-dihydro-5H-dibenzo[a,d]cyclohep ten-5,10-imine maleate ([H-3]MK-801), [H-3]glutamate and [H-3]glycine to the rat and monkey striatal N-methyl-D-aspartate (NMDA) receptor. W e found that MPP(+) non-competitively inhibits [H-3]MK-801 binding wit h IC50 values between 80 and 330 mu M depending on the species and the concentration of glutamate and glycine. MPP(+) also partially inhibit ed [3H]glycine binding without affecting [H-3]glutamate binding. We co nclude that MPP(+) is not an agonist at the NMDA receptor but at high concentrations inhibits NMDA receptor function.