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 Kd of 290 nM and a Bmax 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.
D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism / Q000494:pharmacology; D001575:Benzomorphans / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism* / Q000494:pharmacology; D006220:Haloperidol / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000378:metabolism; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D010627:Phenethylamines / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000378:metabolism*; D013347:Subcellular Fractions / Q000737:chemistry / Q000378:metabolism; D014316:Tritium