ifenprodil

Ifenprodil hemitartrate is a NMDA receptor antagonist, acting at the polyamine site. Also anα-adrenergic vasodilator.σ2ligand displaying about 3-fold selectivity overσ1sites.

Ifenprodil (RC61-91) 是 NMDA 受体抑制剂，特别是 GluN1(甘氨酸结合 NMDA 受体亚基 1)和 GluN2B(谷氨酸结合 NMDA 受体亚基 2)亚基的抑制剂。此外，它抑制 GIRK 通道并与 α1 肾上腺素能、血清素和 sigma 受体相互作用。

Ifenprodil tartrate 是典型的非竞争性 NMDA 受体拮抗剂，抑制 GIRK (Kir3)，通过基底 GIRK 活性减少内向电流，有用做脑血管舒张试剂的潜力。它对 NR1A NR2B 受体亲和力是 NR1A NR2A 受体的 400 倍。

Ifenprodil glucuronide, a derivative of Ifenprodil, is a vasodilator and an inhibitor of platelet aggregation. In contrast to Ifenprodil, Ifenprodil glucuronide does not affect platelet aggregation nor arterial contraction.

σ receptor agonist and NR2B subunit-selective NMDA receptor antagonist

Arcaine sulfate 是一种多胺，是 N-甲基-d-天冬氨酸 (NMDA) 受体多胺结合位点的拮抗剂。 Arcaine 是一种胍丁胺类似物，与 ifenprodil 一起，可能有可能用于治疗癫痫疾病。

WMS-1405是ifenprodil的衍生物。作为一种高效的NR2B选择性NMDA受体拮抗剂，WMS-1405展示出了5.4 nM的Ki值。通过中心构建基块合成，WMS-1405由于其基本氮原子与苯基残基之间的特定距离，显示出高NR2B亲和性。WMS-1405具有成为治疗兴奋毒性的NMDA拮抗剂的潜力。

Sepimostat dimethanesulfonate (FUT-187) exhibits neuroprotective activity via NR2B N-methyl-D-aspartate receptor antagonism at the Ifenprodil-binding site of the NR2B subunit. Sepimostat dimethanesulfonate inhibits the Ifenprodil binding with a Ki value of 27.7 μM[1]. Sepimostat (1 to 100 nmol eye, intravitreal injection) exhibits significant neuroprotective effect[1]. Animal Model: Male Sprague Dawley rats weighing 150-300 g[1]. [1]. Masahiro Fuwa, et al. Nafamostat and Sepimostat Identified as Novel Neuroprotective Agents via NR2B N-methyl-D-aspartate Receptor Antagonism Using a Rat Retinal Excitotoxicity Model. Sci Rep. 2019 Dec 31;9(1):20409.

Ro 04-5595 is a selective antagonist of NMDA receptors NR2B subunits. Ro 04-5595 had an EC 50 of 186 ± 32 nmol L. Ro 04-5595 was predicted to bind the EVT-101 binding site, not the ifenprodil-binding site. Specific binding, defined with a new NR2B-specific antagonist Ro 04-5595 at 10 microM was fully inhibited by several compounds with the following rank order of affinities--Ro 25-6981 > CP-101,606 > Ro 04-5595 = ifenprodil >> eliprodil > haloperidol > spermine > spermidine > MgCl2 > CaCl2--and partially inhibited by competitive glutamate recognition site antagonists. Complementary high-resolution autoradiographic images using [3H]Ro04-5595 demonstrated strong binding in NR2B receptor-rich regions and low binding in cerebellum where NR2B concentration is low.

EVT-101 is a GluN2B antagonist, binding at the same GluN1 GluN2B dimer interface as ifenprodil but adopting a remarkably different binding mode involving a distinct subcavity and receptor interactions.

Sepimostat 通过 NR2B 亚基的 Ifenprodil 结合位点的 NR2B N-甲基-D-天冬氨酸受体拮抗作用表现出神经保护活性。它抑制 Ifenprodil 结合的 Ki 值为27.7 µM。