Subunit arrangement and phenylethanolamine binding in GluN1/GluN2B NMDA receptors

Ifenprodil, a phenylethanolamine first developed as an adrenergic antagonist and now widely used as an antihypertensive, also has a neuroprotective effect through receptors. A study of this interaction shows that the NMDA receptor subunits GluN1 and GluN2B form heterodimers that bind ifenprodil at the GluN1/GluN2B interface. Conformational mobility in the GluN2B amino-terminal domain is essential for ifenprodil-mediated inhibition of the NMDA receptors. These findings may be relevant to the design of therapeutics to target specific NMDA receptor subtypes for use in neurological disorders.