Binding of [³H]desglycinyl remacemide to rat brain membranes: Association with the benzomorphan attachment site of the N-methyl-D-aspartic acid receptor channel

Desglycinyl remacemide (DGR), a biologically active metabolite of remacemide, was radiolabeled in an attempt to develop a ligand binding assay to identify its site of action. Incubation of the radioligand with membranes obtained from P₂ fractions of whole rat brain revealed a single population of specific [³H]-DGR binding sites having a K(d) of 290 nM and a B(max) of 1.3 pmole/mg protein. The specific binding of [³H]-DGR is most enriched in the P₂ subcellular fraction and is heterogeneously distributed throughout the brain. The binding of [³H]-DGR to rat brain membranes was inhibited most potently by MK-801 and SKF-10,047. In contrast, haloperidol, and other sigma receptor-active agents, were relatively inactive at this site. These data suggest that DGR interacts with a channel blocking site on the NMDA receptor.