WMS-1410 

WMS-1410 is a selective GluN2B-containing NMDA receptor inhibitor with an IC₅₀ of 18.4 nM. WMS-1410 regulates intracellular calcium levels and protects cells from Apoptosis. WMS-1410 inhibits glutamate-induced excitotoxicity. WMS-1410 reverses NMDA/glycine-induced reduction in glucose-stimulated insulin secretion without altering physiological insulin secretion or baseline redox status, but fails to counteract insulin content loss induced by glucolipotoxicity. WMS-1410 exhibits analgesic activity against advanced neuropathic pain. WMS-1410 can be used in studies related to stroke, brain injury, Alzheimer's disease, Parkinson's disease, type 2 diabetes, and neuropathic pain^[1][2][3].

When incubated with rat liver microsomes and NADPH/H⁺, WMS-1410 (300 μg; 120 min) generates four distinct phase I hydroxylated metabolites via modification of its butyl chain, phenylbutyl benzene ring, aliphatic azepine skeleton, and aromatic benzazepine ring^[1].
Following incubation with rat liver microsomes and phase II conjugation cofactors, WMS-1410 (300 μg; 120 min) generates 2 direct phase II conjugation metabolites and 5 phase I/II combined metabolites via glucuronidation, sulfation and methylation reactions^[1].
WMS-1410 (150 μg; 15-60 min) exhibits high metabolic stability in rat liver microsomes, with 93% of the compound remaining intact after 60 min of incubation^[1].
WMS-1410 potently binds to NMDA receptors containing the GluN2B subunit, with a K_i value of 13 nM and an IC₅₀ value of 18.4 nM for inhibiting receptor activity^[1].
WMS-1410 (1 μM; 48 h) completely inhibits NMDA-induced oxidative stress in mouse islet cells after 48 hours of co-incubation^[2].
WMS-1410 (0.1-1 μM; 18 h) partially attenuates NMDA/glycine-induced apoptotic death of mouse islet cells after 18 h of co-incubation^[2].
WMS-1410 (1 μM; 24 h) completely blocks NMDA-induced impairment of glucose-stimulated insulin secretion in mouse islets after 24 h of co-incubation^[2].
WMS-1410 (0.1-1 μM; 7 d) reduces palmitate-mediated glucolipotoxicity-induced apoptosis of mouse islet cells in a dose-dependent manner after 7 days of co-incubation^[2].
WMS-1410 (1 μM) reduces the proportion of mouse islet cells that exhibit elevated intracellular calcium levels in response to acute NMDA/glycine treatment^[2].
WMS-1410 (6 different concentrations; 120 min) binds to the Ifenprodil (HY-12882) binding site of L (tk⁻) cell membrane homogenates expressing NR1a/NR2B with a K_i value of 14 nM, exhibits excellent selectivity for σ₂ receptors, and shows no significant binding to the PCP binding site of NMDA receptors^[3].
WMS-1410 (1 nM-10 μM; 30 min preincubation, 4 h incubation with glutamate/glycine) inhibits glutamate/glycine-induced excitotoxicity in L13-E6 cells expressing NR1a/NR2B, with an IC₅₀ of 18.4 nM, and exhibits only extremely low activity in cells expressing NR1a/NR2A^[3].
WMS-1410 exhibits high selectivity for NR2B-containing NMDA receptors, with its selectivity surpassing that of over 100 tested receptors, transporters and enzymes, and only showing weak activity at the CGRP₁ receptor and hERG channel^[3].
WMS-1410 exhibits better metabolic stability than Ifenprodil in mouse and rat liver microsomes, with half-lives of 28 min and <3 min^[3], respectively.

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

WMS-1410 (7.8 mg/kg; i.p.; single dose) undergoes in vivo biotransformation in female Wistar rats primarily via glucuronidation of its phenolic moiety, with additional hydroxylation, methylation, and combined phase I/II reactions, and shows higher metabolic stability than ifenprodil^[1].
WMS-1410 (10-100 mg/kg; i.p.; single dose) exhibits dose-dependent analgesic activity in the late neuropathic pain phase of the mouse formalin assay, with the lowest active dose being 30 mg/kg^[3].
WMS-1410 (1-100 mg/kg; i.p.; single dose) is well tolerated in mice at intraperitoneal doses up to 100 mg/kg, with only mild diarrhea observed at the highest tested dose^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

311.42

C₂₀H₂₅NO₂

1253197-38-4

OC1=CC=C2C(CCN(CC2O)CCCCC3=CC=CC=C3)=C1

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Falck E, et al. In vitro and in vivo biotransformation of WMS-1410, a potent GluN2B selective NMDA receptor antagonist. J Pharm Biomed Anal. 2014;94:36-44.

  [2]. Gresch A, et al. Selective Inhibition of N-Methyl-d-aspartate Receptors with GluN2B Subunit Protects β Cells against Stress-Induced Apoptotic Cell Death. J Pharmacol Exp Ther. 2021;379(3):235-244.

  [3]. Tewes B, et al. Conformationally constrained NR2B selective NMDA receptor antagonists derived from ifenprodil: Synthesis and biological evaluation of tetrahydro-3-benzazepine-1,7-diols. Bioorg Med Chem. 2010;18(22):8005-8015.