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| Targets |
Evenamide selectively blocks voltage-gated sodium channels (VGSCs) in a voltage- and use-dependent manner with a Ki of 0.4 μM. The compound modulates sustained repetitive firing without inducing impairment of normal neuronal excitability. Evenamide does not bind to more than 130 different receptors, ion channels, and enzymes, indicating a highly selective mechanism of action. The compound is also a monoamine oxidase B (MAO-B) inhibitor.
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| ln Vitro |
Evenamide regulates prolonged repeated firing and selectively blocks voltage-gated sodium channels (VGSC) (Ki=0.4 µM) in a manner that is dependent on usage and voltage, all without impairing normal neuronal excitability. More than 130 different receptors, enzymes, and transporters are not bound, inhibited, or interacted with by evenamide [2].
In vitro, evenamide selectively blocks voltage-gated sodium channels (VGSCs) in a voltage- and use-dependent manner with a Ki of 0.4 μM. The compound modulates sustained repetitive firing without impairing normal neuronal excitability. Evenamide's unique mechanism of action targets abnormal electrical activity and glutamatergic abnormalities. The compound does not bind to a wide range of neurotransmitter receptors, contributing to its favorable side effect profile. |
| ln Vivo |
In a variety of animal models used in psychotherapy, evenamide is effective when used alone or in combination with antipsychotics. Cl 395 (PCP) lesioned rats (MED=1 mg/kg po) show significant improvement in social interaction deficits when evenamide is administered[2].
In vivo, evenamide shows efficacy in a broad spectrum of rodent models of psychosis, mania, depression, and aggressiveness. The compound's efficacy in downregulating the hyperdopaminergic state, social deficits, and recognition memory impairment may result from its ability to attenuate ventral hippocampal hyperexcitability. Evenamide is capable of addressing positive, cognitive, and negative symptoms of schizophrenia. Clinical studies have demonstrated efficacy in treatment-resistant schizophrenia patients. |
| Enzyme Assay |
Non-cellular enzyme assays for evenamide involve assessing its binding affinity for voltage-gated sodium channels using radioligand binding displacement studies. Membrane preparations from brain tissue or cells expressing VGSCs are incubated with a radiolabeled sodium channel ligand (e.g., [³H]batrachotoxin) and varying concentrations of evenamide. Binding displacement curves are generated to determine Ki values. MAO-B inhibition is assessed using a radioenzymatic assay with the substrate ¹⁴C-phenylethylamine (PEA).
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| Cell Assay |
In vitro cellular assays for evenamide involve treating neuronal cultures or cells expressing VGSCs with the compound and measuring sodium channel activity using patch-clamp electrophysiology. Whole-cell voltage-clamp recordings are performed to assess the voltage- and use-dependent block of sodium currents. Cells are depolarized at various frequencies and holding potentials in the presence of increasing concentrations of evenamide. The reduction in sodium current amplitude is quantified to construct concentration-response curves and determine the Ki.
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| Animal Protocol |
In vivo animal experiments with evenamide are conducted in rodent models of schizophrenia and psychosis. Mice or rats are treated with evenamide via oral or intraperitoneal administration, and behavioral assays are performed. These include prepulse inhibition (PPI) of startle, amphetamine-induced hyperlocomotion, social interaction tests, and cognitive function tests such as novel object recognition. The compound's effects on positive, cognitive, and negative symptoms are assessed in these models.
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| ADME/Pharmacokinetics |
Evenamide has a molecular weight of 328.4 and a molecular formula of C₁₇H₂₄N₂O₄. It is a solid at room temperature with a purity of ≥98%. The compound is soluble in DMSO and other organic solvents. It is typically stored at -20°C, protected from light and moisture. Evenamide is orally bioavailable and has shown favorable pharmacokinetic properties in preclinical and clinical studies, supporting once- or twice-daily dosing.
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| Toxicity/Toxicokinetics |
Evenamide is generally well-tolerated in preclinical and clinical studies. The compound's selective mechanism of action targeting VGSCs without affecting normal neuronal excitability suggests a favorable side effect profile. In clinical trials, evenamide has demonstrated a low incidence of extrapyramidal symptoms and metabolic side effects commonly associated with antipsychotic medications. Standard laboratory safety precautions should be followed when handling the compound.
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| References | |
| Additional Infomation |
Drug Indication
Treatment of schizophrenia Evenamide (NW-3509; CAS 1092977-61-1) is a first-in-class voltage-gated sodium channel modulator being developed for the treatment of schizophrenia, including treatment-resistant schizophrenia. It selectively blocks VGSCs in a voltage- and use-dependent manner with a Ki of 0.4 μM. Evenamide shows efficacy in rodent models of psychosis, mania, depression, and aggressiveness. The compound is being developed by Newron Pharmaceuticals and has completed Phase 2/3 clinical trials. |
| Molecular Formula |
C16H26N2O2
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|---|---|
| Molecular Weight |
278.4
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| Exact Mass |
278.199
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| CAS # |
1092977-61-1
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| PubChem CID |
25105689
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| Appearance |
Colorless to light yellow liquid
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| Density |
1.0±0.1 g/cm3
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| Boiling Point |
412.1±30.0 °C at 760 mmHg
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| Flash Point |
203.0±24.6 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.510
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| LogP |
2.38
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
20
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| Complexity |
269
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C1=CC=CC(=C1)CCNCC(N(C)C)=O)CCCC
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| InChi Key |
GRHBODILPPXVKN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H26N2O2/c1-4-5-11-20-15-8-6-7-14(12-15)9-10-17-13-16(19)18(2)3/h6-8,12,17H,4-5,9-11,13H2,1-3H3
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| Chemical Name |
2-[2-(3-butoxyphenyl)ethylamino]-N,N-dimethylacetamide
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| Synonyms |
NW3509; NW 3509; NW-3509
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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 : ~100 mg/mL (~359.21 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.98 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.98 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (8.98 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5920 mL | 17.9598 mL | 35.9195 mL | |
| 5 mM | 0.7184 mL | 3.5920 mL | 7.1839 mL | |
| 10 mM | 0.3592 mL | 1.7960 mL | 3.5920 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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