Modular organization of NR2B subunit of NMDA receptor. A. Diagram shows the amino-terminal domain (ATD), the two lobes (S1–S2) comprising the glutamate binding domain, the three transmembrane domains (M1, M3 and M4), the re-entrant loop and the intracellular cytoplasmic terminus (-COOH). ATD has been proposed to harbor the binding site for phenylethanolamines such as ifenprodil. B. Chemical structures of ifenprodil, RO25,6981 and haloperidol – ligands that bind to and negatively modulate the current flux through NR2B subunit-containing NMDA receptors.