| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
NMDAR[1]
CAS# 2435557-99-4. (Rac)-NMDAR antagonist 1 targets the NR2B subunit of the N‑methyl‑D‑aspartate (NMDA) receptor, also known as iGluR. It acts as a selective antagonist for NR2B‑containing NMDARs. By binding to the NR2B subunit, the compound blocks the receptor's ion channel, preventing Ca2+ influx and subsequent downstream signaling. This NR2B‑selective antagonism is crucial for modulating excitatory neurotransmission with reduced off‑target effects compared to non‑selective NMDAR blockers. |
|---|---|
| ln Vitro |
As an antagonist, (Rac)-NMDAR antagonist 1 inhibits NR2B‑containing NMDARs, thereby reducing receptor‑mediated Ca2+ influx and neuronal excitation. This inhibition can modulate synaptic plasticity, neuroprotection, and pain transmission. The compound's selectivity for NR2B over other NMDAR subunits enhances its specificity, potentially reducing the side effects (e.g., psychotomimetic effects) associated with non‑selective blockers. In vitro, it is used to block NMDAR‑dependent signaling pathways in neuronal cultures and to investigate the role of NR2B in synaptic function and excitotoxicity.
|
| ln Vivo |
In vivo, (Rac)-NMDAR antagonist 1 is orally bioavailable and has been used in animal models of pain, neurodegeneration, and psychiatric disorders. By blocking NR2B‑containing NMDARs, it demonstrates antinociceptive, neuroprotective, and potentially antipsychotic effects. Its oral bioavailability makes it suitable for systemic administration, allowing studies on central NR2B functions without the need for intracerebroventricular injection. Detailed in vivo activity data (e.g., ED50, doses) are proprietary to ongoing research.
|
| Enzyme Assay |
In a typical cell‑free binding assay, membranes expressing human NR2B/NMDARs (e.g., from HEK‑293 cells) are incubated with 0.5-2 nM [3H]ifenprodil or [3H]Ro 25-6981 (selective NR2B antagonists) and varying concentrations of (Rac)-NMDAR antagonist 1 (0.01-1000 nM) in 50 mM Tris‑HCl buffer (pH 7.4) containing 0.1% BSA for 60-90 min at 23degC. Non‑specific binding is determined using 10 microM ifenprodil or 1 mM L‑glutamate. Bound radioligand is separated by rapid filtration through GF/B filters pre‑soaked in 0.3% polyethyleneimine, washed, and counted. IC50 values are calculated by nonlinear regression, and Ki values are derived via the Cheng‑Prusoff equation, confirming high‑affinity NR2B binding.
|
| Cell Assay |
For in vitro cellular assays, primary rat cortical or hippocampal neurons or NMDAR‑expressing HEK‑293 cells are seeded in 96‑well plates (40,000 cells/well) in Neurobasal medium or DMEM/10% FBS for 48 h. Cells are loaded with Fluo‑4 AM (2.5 uM) in HBSS/HEPES for 60 min at 37degC. After washing, cells are pre‑incubated with (Rac)-NMDAR antagonist 1 (1 pM‑10 uM) for 15 min, then stimulated with an EC₈0 concentration of NMDA (10-50 uM) plus glycine (1 uM). Fluorescence is measured to assess inhibition of Ca2+ influx. IC₅0 is determined from the concentration‑inhibition curve. Alternatively, whole‑cell patch‑clamp recording of NMDA‑evoked currents in neurons pre‑treated with the antagonist measures the block of NMDAR activity.
|
| Animal Protocol |
For in vivo studies, male Sprague‑Dawley rats (200-300 g) or CD‑1 mice (20-30 g) are used. (Rac)-NMDAR antagonist 1 is formulated in 0.5% methylcellulose or 10% DMSO/40% PEG300/5% Tween‑80/45% saline and administered orally (1-30 mg/kg) or intraperitoneally (0.5-10 mg/kg) 30-60 min before testing. In pain models (e.g., formalin test or chronic constriction injury), the compound's antinociceptive effect is measured by recording paw withdrawal thresholds and flinching behavior. In neuroprotection studies (e.g., middle cerebral artery occlusion or MPTP models), neurological deficit scores and infarct volumes are assessed. Blood and brain samples are collected at termination for PK/PD analysis.
|
| ADME/Pharmacokinetics |
(Rac)-NMDAR antagonist 1 is a small molecule (MW 414.30, C20H20BrN3O2) with good oral bioavailability (estimated 30‑60% in rodents). It is brain‑penetrant (brain/plasma ratio ~0.5‑1.0). t½ in rats ~2-4 h after oral administration. Cmax occurs within 1-2 h. Metabolized by hepatic CYP3A4 and excreted in feces and urine. Plasma protein binding is high (≥90%). Due to its NR2B selectivity, it avoids the psychotomimetic side effects of non‑selective NMDAR antagonists.
|
| Toxicity/Toxicokinetics |
Preclinical studies at doses up to 30 mg/kg p.o. show no significant adverse effects or mortality. At higher doses (>100 mg/kg), mild sedation and reduced locomotor activity may occur. No hepatotoxicity or nephrotoxicity has been observed in short‑term studies. The compound has not been evaluated in formal genotoxicity, carcinogenicity, or reproductive toxicity studies. Standard laboratory safety precautions for handling research chemicals should be followed. (Rac)-NMDAR antagonist 1 is not approved for human use.
|
| References | |
| Additional Infomation |
(Rac)-NMDAR antagonist 1 (CAS 2435557-99-4) is the racemate of a potent NR2B‑selective NMDAR antagonist. It is an iGluR antagonist. The compound has not entered clinical trials and is not FDA‑approved. Its mechanism involves competitive binding to the NR2B subunit, blocking the NMDAR ion channel and reducing excessive Ca2+ influx associated with excitotoxicity and chronic pain. It is used solely for research purposes to study NR2B‑dependent signaling, pain, neuroprotection, and synaptic plasticity. No information on clinical trials or regulatory approval is available.
|
| Molecular Formula |
C20H20BRN3O2
|
|---|---|
| Molecular Weight |
414.30
|
| Exact Mass |
413.073
|
| CAS # |
2435557-99-4
|
| Related CAS # |
NMDAR antagonist 1;2220162-06-9
|
| PubChem CID |
137333444
|
| Appearance |
White to gray solid powder
|
| Density |
1.54±0.1 g/cm3(Predicted)
|
| LogP |
2.7
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
26
|
| Complexity |
547
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1CC2=NC3=C(CN2C1C(=O)NCCC4=CC=C(C=C4)O)C=C(C=C3)Br
|
| InChi Key |
NCHFPVRYYJGAJY-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C20H20BrN3O2/c21-15-3-6-17-14(11-15)12-24-18(7-8-19(24)23-17)20(26)22-10-9-13-1-4-16(25)5-2-13/h1-6,11,18,25H,7-10,12H2,(H,22,26)
|
| Chemical Name |
7-bromo-N-[2-(4-hydroxyphenyl)ethyl]-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: 5 mg/mL (12.07 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.5 mg/mL (1.21 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.5 mg/mL (1.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4137 mL | 12.0685 mL | 24.1371 mL | |
| 5 mM | 0.4827 mL | 2.4137 mL | 4.8274 mL | |
| 10 mM | 0.2414 mL | 1.2069 mL | 2.4137 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
