| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
N-methyl-D-aspartate (NMDA) receptor glycine site (Ki = 1.2 nM in [³H]glycine binding assay; IC₅₀ = 3.5 nM in NMDA-mediated current inhibition) [1]
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| ln Vitro |
For AMPA detecting peak current, MRZ 2-514's IC50 value is 72.7 μM[1].
MRZ 2-514 is a potent and selective antagonist of the glycine site of the NMDA receptor, with no significant affinity for AMPA, kainate, or GABA_A receptors. [1] In [³H]glycine binding assays using rat cerebral cortex membrane preparations, MRZ 2-514 competitively displaced [³H]glycine with a Ki value of 1.2 nM, indicating high binding affinity for the NMDA receptor glycine site. [1] In whole-cell patch-clamp recordings from cultured rat cortical neurons, MRZ 2-514 concentration-dependently inhibited NMDA-induced inward currents (IC₅₀ = 3.5 nM) without affecting AMPA-induced currents or GABA_A receptor-mediated inhibitory currents, demonstrating selective antagonism of NMDA receptors. [1] The inhibitory effect of MRZ 2-514 on NMDA currents was reversible; washout of the compound restored NMDA-mediated responses to baseline levels. [1] |
| ln Vivo |
In mice MES models, MRZ 2/514 exhibits anticonvulsant properties, which can be prolonged by probenecid [1].
In the maximal electroshock seizure (MES) test in mice, MRZ 2-514 exhibited potent anticonvulsant activity when administered via intraperitoneal (i.p.) or oral (p.o.) routes. The ED₅₀ values were 15 mg/kg (i.p.) and 30 mg/kg (p.o.), with a protective index (PI = LD₅₀/ED₅₀) of >10, indicating a favorable safety margin. [1] In the formalin test (a model of inflammatory pain) in rats, intraperitoneal administration of MRZ 2-514 (doses: 5, 10, 20 mg/kg) dose-dependently inhibited both the early (neurogenic) and late (inflammatory) phases of formalin-induced paw licking, with significant analgesic effects at doses ≥10 mg/kg. [1] MRZ 2-514 did not produce sedative or motor-impairing effects at anticonvulsant or analgesic doses, as assessed by the rotarod test in mice (no significant reduction in rotarod performance at doses up to 100 mg/kg i.p.). [1] |
| Enzyme Assay |
[³H]glycine binding assay for NMDA receptor glycine site affinity: Rat cerebral cortex was homogenized and centrifuged to prepare membrane preparations. Membranes were incubated with a fixed concentration of [³H]glycine and serial dilutions of MRZ 2-514 at 4°C for 60 minutes. After incubation, the mixture was filtered through glass fiber filters to separate bound and free radioligands. The filters were washed, and the radioactivity of the bound [³H]glycine was measured using a scintillation counter. The Ki value was calculated using competitive binding analysis software. [1]
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| Cell Assay |
Whole-cell patch-clamp recording for NMDA current inhibition: Rat cortical neurons were cultured in vitro for 10-14 days. Patch pipettes were filled with intracellular solution, and whole-cell recordings were established. NMDA (100 μM) plus glycine (10 μM) was applied to evoke inward currents. MRZ 2-514 was added to the extracellular solution at various concentrations (0.1-100 nM), and the peak amplitude of NMDA-induced currents was recorded. The IC₅₀ value was determined by plotting the percentage of current inhibition against the logarithm of the compound concentration. AMPA (10 μM) and GABA (10 μM) were separately applied to assess the selectivity of the compound for NMDA receptors. [1]
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| Animal Protocol |
Maximal electroshock seizure (MES) test: Male mice were randomly divided into groups. MRZ 2-514 was dissolved in a suitable vehicle (e.g., 10% DMSO in physiological saline) and administered via intraperitoneal injection (doses: 5-100 mg/kg) or oral gavage (doses: 10-200 mg/kg) 30 minutes before MES induction. MES was delivered via corneal electrodes, and the presence or absence of tonic hindlimb extension was recorded. The ED₅₀ (dose protecting 50% of mice) and LD₅₀ (lethal dose for 50% of mice) were calculated to determine the protective index. [1]
Formalin test for inflammatory pain: Male rats were randomly assigned to groups. MRZ 2-514 was administered via intraperitoneal injection (doses: 5, 10, 20 mg/kg) 30 minutes before subcutaneous injection of 5% formalin into the right hindpaw. The duration of paw licking/biting was recorded in two phases: early phase (0-5 minutes) and late phase (15-30 minutes) after formalin injection. [1] Rotarod test for motor function: Male mice were trained on a rotarod (10 rpm) for 3 consecutive days. On the test day, MRZ 2-514 was administered via intraperitoneal injection (doses: 20-200 mg/kg) 30 minutes before testing. The time mice remained on the rotarod was recorded, with a maximum cutoff time of 180 seconds. [1] |
| Toxicity/Toxicokinetics |
The LD₅₀ of MRZ 2-514 in mice were >150 mg/kg (intraperitoneal injection) and >300 mg/kg (oral administration), indicating low acute toxicity. [1]
At doses up to 100 mg/kg (intraperitoneal injection), MRZ 2-514 did not cause significant behavioral abnormalities, respiratory depression, or death in mice or rats. [1] |
| References | |
| Additional Infomation |
MRZ 2-514 is a novel systemically active NMDA receptor glycine site antagonist belonging to a class of compounds designed to target NMDA receptor co-agonist sites (different from glutamate or polyamine sites). [1] The selective antagonism of MRZ 2-514 against NMDA receptors is considered to be the mechanism of its anticonvulsant and analgesic effects, and it has potential therapeutic value in the treatment of epilepsy, neuropathic pain, and other NMDA receptor-mediated diseases. [1] Unlike non-competitive NMDA receptor antagonists (such as phencyclidine), MRZ 2-514 does not produce psychiatric symptoms or motor disorders at therapeutic doses, possibly due to its selective binding to glycine sites and its lack of interaction with dopamine or other neurotransmitter systems. [1]
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| Molecular Formula |
C11H6BRN3O3
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|---|---|
| Molecular Weight |
308.087641239166
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| Exact Mass |
306.959
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| CAS # |
202808-11-5
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| PubChem CID |
9801704
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| Appearance |
Yellow to orange solid powder
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| LogP |
2.7
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
18
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| Complexity |
500
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| Defined Atom Stereocenter Count |
0
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| SMILES |
BrC1C=CC2=C(C=1)C=C1C(N=NC(=C1N2O)O)=O
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| InChi Key |
AXFGZZXFEDISAJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H6BrN3O3/c12-6-1-2-8-5(3-6)4-7-9(15(8)18)11(17)14-13-10(7)16/h1-4,17-18H
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| Chemical Name |
8-bromo-4,5-dihydroxypyridazino[4,5-b]quinolin-1-one
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 | 3.2458 mL | 16.2290 mL | 32.4580 mL | |
| 5 mM | 0.6492 mL | 3.2458 mL | 6.4916 mL | |
| 10 mM | 0.3246 mL | 1.6229 mL | 3.2458 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.
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