MDL 105519 is a potent and specific antagonist of glycine binding to NMDA receptors.

Physicochemical Properties

Molecular Formula	C18H11CL2NO4
Molecular Weight	376.18
Exact Mass	375.006
CAS #	161230-88-2
Related CAS #	(Z)-MDL 105519;179105-67-0
PubChem CID	6603913
Appearance	Off-white to yellow solid powder
Density	1.6±0.1 g/cm3
Boiling Point	601.3±55.0 °C at 760 mmHg
Flash Point	317.5±31.5 °C
Vapour Pressure	0.0±1.8 mmHg at 25°C
Index of Refraction	1.764
LogP	5.87
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	25
Complexity	561
Defined Atom Stereocenter Count	0
SMILES	C1=CC=C(C=C1)/C(=C\C2=C(NC3=C2C(=CC(=C3)Cl)Cl)C(=O)O)/C(=O)O
InChi Key	LPWVUDLZUVBQGP-DHZHZOJOSA-N
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+
Chemical Name	3-[(E)-2-carboxy-2-phenylethenyl]-4,6-dichloro-1H-indole-2-carboxylic acid
Synonyms	MDL105519; MDL 105519; MDL-105519
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)

Biological Activity

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].
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].
References	[1]. Pharmacological characterization of MDL 105,519, an NMDA receptor glycine site antagonist. Eur J Pharmacol. 1997 Apr 4;323(2-3):181-92.

Solubility Data

Solubility (In Vitro)

DMSO : ~17 mg/mL (~45.19 mM)

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (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.