| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
MDL-105519 targets the glycine binding site of the NMDA receptor. It acts as a selective, non-competitive antagonist at this site. The compound inhibits [³H]glycine binding to rat brain membranes with a Ki of 10.9 nM and a Kd of 3.89 nM. MDL-105519 is a ligand selective for the glycine recognition site.
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| ln Vitro |
MDL 105519 totally blocks the binding of [3H]glycine to rat meninges, with a Ki value of 10.9 nM. It is a powerful and selective ligand for the glycine recognition site. Comparing MDL 105519 to other receptor types under study, there is a roughly 10,000-fold increase in selectivity for the glycine recognition site. The NMDA-dependent reactions that are inhibited by MDL 105519 include alterations in cytosolic Ca2+ and Na+-Ca2+ currents in cultured neurons, increased [3H]TCP binding in meninges, and buildup of cyclic GMP in brain slices. It can be overcome by D-serine and the inhibition is non-competitive with NMDA [1].
In vitro, MDL-105519 potently inhibits [³H]glycine binding to the NMDA receptor with a Ki of 10.9 nM and a Kd of 3.89 nM. It completely blocks the binding of [³H]glycine to rat brain membranes. The compound inhibits cyclic GMP accumulation in brain slices and modulates Ca²⁺ and Na⁺-Ca²⁺ currents. |
| ln Vivo |
An antagonist of NMDA receptors in vivo is MDL 105519. By preventing the cameline-stimulated increase in cerebellar ring GMP content, MDL 105519 administered intravenously demonstrated NMDA receptor antagonistic activity in vivo. In epilepsy models that are genetically based, chemically generated, or electrically driven, this antagonistic relationship is linked to anticonvulsant activity. In a vocalization model created via rat separation, anxiolytic action was seen, but at lower levels, muscle relaxant activity was also noticeable. Increased dosages reduce rotarod performance but have no effect on prepulse suppression of the startle reflex or mesolimbic dopamine turnover [1].
In vivo, MDL-105519 exhibits anxiolytic activity in rat models. As a selective NMDA receptor glycine site antagonist, it modulates glutamatergic neurotransmission. The compound's effects on cyclic GMP accumulation and ion currents observed in vitro translate to behavioral effects in animal models of anxiety. |
| Enzyme Assay |
The in vitro receptor binding assay for MDL-105519 involves measuring its ability to displace [³H]glycine binding to rat brain membranes. Rat meninges or whole brain membranes are prepared and incubated with [³H]glycine and varying concentrations of MDL-105519. Bound radioactivity is measured by filtration and scintillation counting. The inhibition constant (Ki) is calculated from competition binding curves. MDL-105519 completely inhibits [³H]glycine binding with a Ki of 10.9 nM.
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| Cell Assay |
In vitro cellular assays for MDL-105519 typically involve treating cultured neurons or brain slices with varying concentrations of the compound. NMDA receptor-mediated currents are measured using electrophysiological techniques (patch-clamp). Cyclic GMP accumulation in brain slices is measured by radioimmunoassay. MDL-105519 inhibits cyclic GMP accumulation and modulates Ca²⁺ and Na⁺-Ca²⁺ currents.
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| Animal Protocol |
In vivo animal experiments for MDL-105519 typically use rat models of anxiety, such as the elevated plus maze or social interaction tests. The compound is administered via intraperitoneal or oral routes at various doses. Anxiolytic-like behavior is assessed by measuring time spent in open arms of the elevated plus maze or social interaction time. Brain levels of the compound and NMDA receptor occupancy may also be measured.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of MDL-105519 have not been extensively characterized in publicly available literature. As a small molecule NMDA receptor antagonist, it is expected to have reasonable blood-brain barrier penetration to reach its central target. The compound's molecular weight is 308.29 (C13H12N2O4S). Specific PK parameters including half-life, bioavailability, and metabolic pathways are not well documented.
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| Toxicity/Toxicokinetics |
Toxicological (toxicology) data for MDL-105519 are limited in publicly available sources. The compound has been studied in preclinical models of anxiety, suggesting a manageable safety profile at effective doses. However, systematic toxicology studies including acute toxicity, repeated-dose toxicity, and genotoxicity have not been well documented. Standard safety pharmacology studies would be required for full toxicological characterization.
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| References | |
| Additional Infomation |
MDL-105519 (CAS#: 161230-88-2) is a potent and selective non-competitive antagonist at the glycine site of the NMDA receptor. It completely blocks [³H]glycine binding to rat brain membranes with a Ki of 10.9 nM. The compound exhibits anxiolytic activity in rat models. MDL-105519 is not approved for clinical use and remains a research tool for studying NMDA receptor glycine site function and anxiety disorders.
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| Molecular Formula |
C18H11CL2NO4
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|---|---|
| Molecular Weight |
376.18
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| Exact Mass |
375.006
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| CAS # |
161230-88-2
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| Related CAS # |
(Z)-MDL 105519;179105-67-0
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| PubChem CID |
6603913
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| Appearance |
Off-white to yellow solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
601.3±55.0 °C at 760 mmHg
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| Flash Point |
317.5±31.5 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.764
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| LogP |
5.87
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
561
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)/C(=C\C2=C(NC3=C2C(=CC(=C3)Cl)Cl)C(=O)O)/C(=O)O
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| InChi Key |
LPWVUDLZUVBQGP-DHZHZOJOSA-N
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| InChi Code |
InChI=1S/C18H11Cl2NO4/c19-10-6-13(20)15-12(16(18(24)25)21-14(15)7-10)8-11(17(22)23)9-4-2-1-3-5-9/h1-8,21H,(H,22,23)(H,24,25)/b11-8+
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| Chemical Name |
3-[(E)-2-carboxy-2-phenylethenyl]-4,6-dichloro-1H-indole-2-carboxylic acid
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| Synonyms |
MDL105519; MDL 105519; MDL-105519
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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) |
DMSO : ~17 mg/mL (~45.19 mM)
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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 | 2.6583 mL | 13.2915 mL | 26.5830 mL | |
| 5 mM | 0.5317 mL | 2.6583 mL | 5.3166 mL | |
| 10 mM | 0.2658 mL | 1.3292 mL | 2.6583 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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