Ifenprodil (hemitartrate)

Ifenprodil is an antagonist of NR1A/NR2B subunit-containing NMDA receptors (IC₅₀ = 340 nM).¹ It is selective for NR1A/NR2B subunit-containing NMDA receptors over those containing NR1A/NR2A or NR1A/NR2C subunits (IC₅₀s = 20 and >100 µM, respectively) but also binds to sigma 1 (σ1) receptors, emopamil binding protein, and fungal C-8 sterol isomerase/ERG2 (K_is = 2, 5, and 1 nM, respectively), as well as α₁ adrenergic receptors (α₁-AR; IC₅₀ = 110 nM), and the serotonin receptor types 5-HT_1A and 5-HT₂ (IC₅₀s = 238 and 610 nM, respectively).^2,3,4 Ifenprodil inhibits infection of MDCK cells by H1N1 and H3N2 influenza isolates in vitro (EC₅₀s = 6.6 and 16.9 µM, respectively).⁵ It increases the production of NGF, BDNF, and GDNF in primary mouse astrocytes when used at a concentration of 150 µM.⁶ Ifenprodil also reduces maximal electroshock seizures in mice (ED₅₀s = 16 and 7 mg/kg, respectively).²

WARNING This product is not for human or veterinary use.

1. Williams, K. Ifenprodil discriminates subtypes of the N-methyl-D-aspartate receptor: Selectivity and mechanisms at recombinant heteromeric receptors. Mol. Pharmacol. 44(4), 851-859 (1993).

2. Zhou, Z.L., Cai, S.X., Whittemore, E.R., et al. 4-Hydroxy-1-[2-(4-hydroxyphenoxy)ethyl]-4-(4-methylbenzyl)piperidine: A novel, potent, and selective NR1/2B NMDA receptor antagonist. J. Med. Chem. 42(15), 2993-3000 (1999).

3. Laggner, C., Schieferer, C., Fiechtner, B., et al. Discovery of high-affinity ligands of σ1 receptor, ERG2, and emopamil binding protein by pharmacophore modeling and virtual screening. J. Med. Chem. 48(15), 4754-4764 (2005).

4. Chenard, B.L., Shalaby, I.A., Koe, B.K., et al. Separation of α1 adrenergic and N-methyl-D-aspartate antagonist activity in a series of ifenprodil compounds. J. Med. Chem. 34(10), 3085-3090 (1991).

5. Jang, Y., Shin, J.S., Lee, J.-Y., et al. In vitro and in vivo antiviral activity of nylidrin by targeting the hemagglutinin 2-mediated membrane fusion of influenza A virus. Viruses 12(5), 581 (2020).

6. Toyomoto, M., Inoue, S., Ohta, K., et al. Production of NGF, BDNF and GDNF in mouse astrocyte cultures is strongly enhanced by a cerebral vasodilator, ifenprodil. Neurosci. Lett. 379(3), 185-189 (2005).