Dapsone analogs as potential polyamine binding site modulators of the N‐methyl‐D‐aspartate receptor complex
ABSTRACT A high-throughput radioligand binding assay was used to screen a series of dapsone analogs for their capacity to displace [3H]-spermidine and [3H]-MK-801 from their respective binding sites on the N-methyl-D-aspartate (NMDA) receptor complex in rat brain homogenates. Dapsone did not alter [3H]-spermidine or [3H]-MK-801 binding, suggesting that the neuroprotective properties that have been attributed to this compound may not be due to modulation of the NMDA receptor complex at the polyamine binding site. In contrast, structural analogs of dapsone, including N-phenyl-1,4-phenyldiamine and 4,4′diaminoazobenzene, effectively displaced [3H]-SPD and [3H]-MK-801. These active dapsone analogs may represent a new class of polyamine binding site ligands that may provide opportunities for the rational design of novel NMDA receptor modulators. Drug Dev. Res. 51:268–272, 2000. © 2001 Wiley-Liss, Inc.