CNS-5161 is a novel NMDA ion channel antagonist that interacts with the NMDA receptor/ion channel site to produce noncompetitive blockade of the effects of glutamate.

Physicochemical Properties

Molecular Formula	C16H18CLN3S2
Molecular Weight	351.91
Exact Mass	352.071
CAS #	160754-76-7
Related CAS #	CNS-5161 hydrochloride;160756-38-7
PubChem CID	192711
Appearance	Typically exists as solid at room temperature
Density	1.25g/cm3
Boiling Point	529.2ºC at 760 mmHg
Flash Point	273.8ºC
Vapour Pressure	2.77E-11mmHg at 25°C
Index of Refraction	1.627
LogP	5.257
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	5
Heavy Atom Count	22
Complexity	380
Defined Atom Stereocenter Count	0
SMILES	ClC1C=CC(SC)=CC=1NC(=N)N(C)C1C=CC=C(SC)C=1
InChi Key	JHVHEDNLONERHY-UHFFFAOYSA-N
InChi Code	InChI=1S/C16H18ClN3S2/c1-20(11-5-4-6-12(9-11)21-2)16(18)19-15-10-13(22-3)7-8-14(15)17/h4-10H,1-3H3,(H2,18,19)
Chemical Name	2-(2-chloro-5-methylsulfanylphenyl)-1-methyl-1-(3-methylsulfanylphenyl)guanidine
Synonyms	CNS 5161; CNS5161; CNS-5161
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	In the mammalian brain, CNS-5161 (CNS 5161) is a novel selective non-competitive antagonist of a subset of NMDA glutamate receptors. In rat brain synaptosomal membrane preparations, CNS-5161 can displace [3H]MK-801 binding with a Ki of 1.8 nM and exhibits strong inhibitory effect on NMDA ion channels in vitro [1].
ln Vivo	CNS-5161 (CNS 5161) inhibited the necrotic effects of exogenous N-methyl-D-aspartate via the intraperitoneal (ip) route with an ED80 of 4 mg/ kg in an in vivo NMDA excitotoxicity paradigm in neonatal rats. A study using CNS-5161 demonstrated that an intraperitoneal dose of 4 mg/kg in DBA/2 mice prevented 91% of audiogenic seizures and that it was neuroprotective in newborn rats following hypoxic/ischemic brain injury [1].
References	[1]. Early clinical experience with the novel NMDA receptor antagonist CNS 5161. Br J Clin Pharmacol. 2002 Mar;53(3):305-11.
Additional Infomation	CNS 5161 is a blocker of the NMDA ion channel and has completed Phase IIa proof of concept clinical trials as a novel compound for the treatment of neuropathic pain. Drug Indication Investigated for use/treatment in migraine and cluster headaches, neuropathy (diabetic), and pain (acute or chronic). Mechanism of Action CNS 5161 is a selective and high affinity N-methyl-D-aspartate (NMDA) receptor antagonist with preferential binding to the activated form of the receptor. CNS 5161 also penetrates the brain well and can be used to label selectively brain NMDA receptors in vivo. A radioactive form of CNS 5161 may be used as an agent to monitor NMDA receptors in the human brain using Positron Emission Tomography ("PET") and "the significance of a selective, validated radiopharmaceutical agent suitable for detecting widespread as well as highly localized changes in the NMDA receptor in the living brain cannot be exaggerated".

Solubility Data

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

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	2.8416 mL	14.2082 mL	28.4164 mL
	5 mM	0.5683 mL	2.8416 mL	5.6833 mL
	10 mM	0.2842 mL	1.4208 mL	2.8416 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.