| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
Nav1.1 channel (partial selective positive modulator). Also affects Nav1.2 and Nav1.5. No effect on Nav1.4, Nav1.6, Nav1.7.
|
|---|---|
| ln Vitro |
By step-wise depolarizing voltages using the whole-cell patchclamp configuration, Lu AE98134 (30 μM) promotes the current mediated by Navv1.1 channel, activates Nav1.5 and, to a lesser extent, Nav1.2, but has no effect on Nav1.4, Nav1.6, and Nav1.7 currents in HEK cells expressing Nav1.1, Nav1.2, Nav1.6, Nav1.5, and Nav1.7[1]. Lu AE98134 (30 μM) lowers the action potential threshold, increasing the excitability of FSINs. Repeated firing of action potentials at specific frequencies is induced by intracellular depolarizing current pulses. In addition, Lu AE98134 increases excitability because each current pulse produces a greater number of spikes (163 in control and 230 in Lu AE98134) [1].
Lu AE98134 (30 microM) promotes current mediated by the Nav1.1 channel. It activates Nav1.5 and, to a lesser extent, Nav1.2, but has no effect on Nav1.4, Nav1.6, or Nav1.7 currents in HEK cells using whole-cell patch-clamp. In FSINs, it decreases action potential threshold and increases repetitive firing. |
| ln Vivo |
Fast spiking inhibitory interneurons (FSINs) from Dlx5/6+/− mice had wider action potentials and a greater depolarized spike threshold, which causes aberrant excitability. Lu AE98134 (30 μM) modulates various characteristics characteristic for NaV1.1 channels, increasing the excitability of FSINs neurons from both normal and Dlx5/6+ /− mice. In mature Dlx5/6+/− mice, selective FSIN activation by Lu AE98134 restores cognitive flexibility[1].
In vivo, Lu AE98134 normalizes the altered firing properties of fast-spiking interneurons (FSINs) in Dlx5/6+/- mice. The selective activation of FSINs by Lu AE98134 restores cognitive flexibility in adult Dlx5/6+/- mice. |
| Enzyme Assay |
Recombinant human Nav1.1 channels are expressed in HEK293 cells. Whole-cell patch-clamp recordings are performed to measure sodium currents. Lu AE98134 is applied at a concentration of 30 microM, and its effect on the current amplitude and voltage-dependence of activation is measured.
|
| Cell Assay |
Fast-spiking inhibitory interneurons (FSINs) are isolated from the brains of Dlx5/6+/- mice and cultured. Whole-cell patch-clamp electrophysiology is performed to measure the excitability of these neurons. Lu AE98134 (30 microM) is applied, and its effect on spike frequency and action potential threshold is assessed.
|
| Animal Protocol |
In vivo, Lu AE98134 is formulated in a suitable vehicle (e.g., 10% DMSO in saline) and administered to adult Dlx5/6+/- mice via intraperitoneal injection. Cognitive flexibility is assessed using behavioral assays such as the Y-maze, attentional set-shifting, or the Morris water maze.
|
| ADME/Pharmacokinetics |
No specific PK data is available. The compound has a molecular weight of 425.5 and is soluble in DMSO. Its ability to cross the blood-brain barrier is not confirmed but is suggested by its in vivo efficacy. Its metabolic stability and half-life are unknown.
|
| Toxicity/Toxicokinetics |
No specific toxicity data is available. As a sodium channel activator, the primary risk is neuronal hyperexcitability, which could lower seizure thresholds. Off-target activation of cardiac Nav1.5 channels could prolong QRS duration and cause arrhythmias.
|
| References | |
| Additional Infomation |
Lu AE98134 is a research tool for studying the role of Nav1.1 channels in schizophrenia and other CNS disorders. It is used to explore the therapeutic potential of enhancing the excitability of fast-spiking inhibitory interneurons.
|
| Molecular Formula |
C21H23N5O3S
|
|---|---|
| Molecular Weight |
425.504022836685
|
| Exact Mass |
425.152
|
| CAS # |
849000-18-6
|
| PubChem CID |
2044236
|
| Appearance |
Light yellow to yellow solid powder
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
30
|
| Complexity |
672
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
S(C1C=CC(=C(C=1)C1=NN=C2C3C=CC=CC=3C(C)=NN12)OC)(NCCCC)(=O)=O
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 250 mg/mL (587.54 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.89 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 20.8 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: ≥ 2.08 mg/mL (4.89 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3502 mL | 11.7509 mL | 23.5018 mL | |
| 5 mM | 0.4700 mL | 2.3502 mL | 4.7004 mL | |
| 10 mM | 0.2350 mL | 1.1751 mL | 2.3502 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
