Dapsone analogs as potential polyamine binding site modulators of the N-methyl-D-aspartate receptor complex

A high-throughput radioligand binding assay was used to screen a series of dapsone analogs for their capacity to displace [H-3]-spermidine and [H-3]-M K-801 from their respective binding sites on the N-methyl-D-aspartate (NMDA ] receptor complex in rat brain homogenates. Dapsone did not alter [H-3]- s permidine or [H-3]-MK-801 binding, suggesting that the neuroprotective prop erties that have been attributed to this compound may not be due to modulat ion 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 [H-3]-SPD and [H-3]-MK-801. The se active dapsone analogs may represent a new class of polyamine binding si te ligands that may provide opportunities for the rational design of novel NMDA receptor modulators. (C) 2001 Wiley-Liss, Inc.