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 P-2 fractions of whole rat brain revealed a single population of specific [H-3]-DGR binding sites having a K-d of 290 nhl and a B-max of 1.3 pmole/mg protein. The specific binding of [H-3]-DGR is most enriched in the P-2 subcellular fraction and is heterogeneously distributed throughout the brain. The binding of [H-3]-DGR to rat brain membranes was inhibited most potently by MK-801 and SKF-10,037. 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. (C) 1999 Elsevier Science B.V. All rights reserved.