In vitro activity: Ifenprodil inhibits NMDA-induced currents at NR1A/NR2B and NR1A/NR2A receptors with IC50 of 0.34 μM and 146 μM in oocytes voltage-clamped at -70 mV. Ifenprodil may act as a weak open-channel blocker of NR1A/NR2A receptors, the degree of inhibition seen with 100 μM Ifenprodil at NR1A/NR2A receptors is not altered by changes in the concentration of extracellular glycine. The inhibitory effect of 1 mM Ifenprodil at NR1A/NR2B receptors is reduced by increasing the concentration of glycine. Ifenprodil (10 μM) inhibits virtually all of the NMDA receptor-evoked current in very young rat cortical neurons that contain a single population of receptors exhibiting a high affinity for glycine. Ifenprodil (10 μM) inhibits both the high-affinity population and a significant proportion of the low-affinity component in older rat cortical neurons, thus revealing three pharmacologically distinct populations of NMDA receptors in single neurons. Ifenprodil antagonizes NMDA receptors in an activity-dependent manner, whilst also increasing the receptor affinity for glutamate recognition-site agonists. Ifenprodil inhibition curves against 10 μM and 100 μM NMDA-evoked currents yielded IC50 values of 0.88 μM and 0.17 μM, respectively. Ifenprodil (3 μM) potentiates to approximately 200% of control levels in rat cultured cortical neurones. Ifenprodil exhibits a 39- and 50-fold higher affinity for the agonist-bound activated and desensitized states of the NMDA receptor, respectively, relative to the resting, agonist-unbound state. Ifenprodil binding to the NMDA receptor results in a 6-fold higher affinity for glutamate site agonists.

Mol Pharmacol. 1993 Oct;44(4):851-9; J Neurosci. 1998 Mar 15;18(6):1935-43.