Novel NMDA ligands that are specific and selective to the NR2B subunits based on the derivatives of 7-methoxy-3-(4-phenylbutyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-1-ol

This invention includes the design and synthesis of ligands that bind selectively and specifically to the NR2B subunit of the NMDA receptor. The NMDA receptor is thought to play a role in the pathophysiology of psychiatric disorders, including depression, stroke, drug addiction, and neuropathic pain. Existing ligands to the NMDA receptor are widely used to treat these conditions.

Researchers at the National Institute of Mental Health (NIMH) have synthesized new ligands based on the 7-methoxy-3-(4-phenylbutyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-1-ol molecule. Binding affinities were checked, and candidate ligands were radiolabeled with an 11C isotope. The radiolabeled compounds were evaluated by PET (positron emission tomography) imaging in rodents. The PET imaging showed that these radioligands bind selectively and specifically to the NR2B receptor.