Ifenprodil and Eliprodil: Neuroprotective NMDA Receptor Antagonists and Calcium Channel Blockers

Publisher Summary This chapter discusses the role of Ifenprodil and Eliprodil as neuroprotective N -methyl- D -aspartate (NMDA) receptor antagonists and calcium channel blockers. The polyamines and ifenprodil or eliprodil interact with their own particular binding sites and allosterically modify the actions of agonists and antagonists at the glutamate and glycine recognition sites. The polyamine-sensitive ifenprodil site is allosterically modified by figands acting at the glycine and glutamate sites of the NMDA receptor. Ifenprodil and polyamines also have opposing effects on the binding of glycine site antagonists. The modulatory effects of ifenprodil at the glycine site appear to be present at NR1 and NR1/NR2B receptor transfects, where the inhibitory effects of ifenprodil are reduced by glycine, and can also be observed at native NMDA receptors. The various glycine–polyamine interactions also predict that the inhibitory effects of glycine antagonists and ifenprodil should synergize, as demonstrated by in vivo dialysis studies. It is found that Ifenprodil and eliprodil block the depolarizing effects or the increased entry of calcium induced by NMDA in cell culture and glutamate or NMDA-induced neurotoxicity.