Size | Price | |
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100mg | ||
250mg | ||
500mg | ||
Other Sizes |
Targets |
IC50: 1.0 nM; Ki: 0.88 nM (NR2B subtype NMDA)[1]
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ln Vitro |
Excellent selectivity over hERG binding (IP=20000 nM) and efficacy at NR2B (Ki=0.88 nM) are achieved by NMDA receptor antagonist 2. In a functional experiment that measures Ca2+ flow in cells expressing recombinant NR1/NR2B receptors, NMDA receptor antagonist 2 is assessed. An MK-499-binding experiment is used to assess selectivity over the hERG-channel[1]. In a functional assay with NR2B-expressing cells, NMDA receptor antagonist 2 is highly powerful (IC50=1.0 nM), and in a binding assay with a homogenized human temporal cortex sample, it remains equipotent (Ki=0.81 nM). Compound 22 demonstrates complete ion flux blockade with KD=0.35 nM in an electrophysiology assay utilizing NR2B receptors. Moreover, Compound 22 demonstrates high selectivity over NR2A (IC50=200 μM), hERG binding (IP=20 μM), α-adrenergic receptors based on Prazosin binding (IC50>100 μM), and CYP P450s, such as CYP3A4, 2C9, and 2D6[1].
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ln Vivo |
NMDA receptor antagonist 2 exhibits good oral bioavailability (F=83%), half-life (T1/2=7.5 hours), and clearance (CL=3.6 mL/min/kg) in dogs in pharmacokinetic investigations including higher species. Additionally, it has a half-life (T1/2) of 1.5 hours and moderate clearance (CL=12 mL/min/kg) as well as oral bioavailability (F=17%) in rhesus[1]. According to a rat pharmacokinetic research, NMDA receptor antagonist 2 has an oral bioavailability of 23%, a half-life of 0.7 hours, and a clearance of 24 milliliters per minute per kilogram. When administered orally, the rat receptor occupancy ED50 is 4.8 mg/kg[ 1]. The surgical closure of two lumbar nerves in the spinal column causes a state of mechanical allodynia in rats used in the spinal nerve ligation model of neuropathic pain[1]. After oral dosing at 10 and 30 mg/kg, NMDA receptor antagonist 2 (oral administration; 3–30 mg/kg) reduces tactile allodynia in a dose-dependent manner. When compared to animals administered with a vehicle, it results in an average improvement in the maximal potential effect of 15% (3 mg/kg), 41% (10 mg/kg), and 69% (30 mg/kg)[1]. NMDA receptor antagonist 2 (oral; 3–30 mg/kg) works well in a Parkinson's disease acute mouse model. When haloperidol is given at a dose that has been demonstrated to cause an initial cataleptic reaction in rats, compound 22 exhibits a dose-dependent reduction in catalepsy scores, with average improvements of 34% (3 mg/kg), 86% (10 mg/kg), and 92% (30 mg/kg) in comparison to the vehicle group[1].
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References |
[1]. Mark E Layton, et al. Discovery of 3-substituted Aminocyclopentanes as Potent and Orally Bioavailable NR2B Subtype-Selective NMDA Antagonists.
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Molecular Formula |
C20H21N7O
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Molecular Weight |
375.43
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CAS # |
875898-41-2
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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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SMILES |
N1C(N[C@@H]2C[C@H](CC2)C2ON=C(N=2)CC2=CC=C(C=C2)C)=C2C=NNC2=NC=1
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HS Tariff Code |
2934.99.9001
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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)
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Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.6636 mL | 13.3181 mL | 26.6361 mL | |
5 mM | 0.5327 mL | 2.6636 mL | 5.3272 mL | |
10 mM | 0.2664 mL | 1.3318 mL | 2.6636 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.