| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
Centanafadine targets the dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT). By binding to these transporters, centanafadine inhibits the reuptake of dopamine, norepinephrine, and serotonin into the presynaptic neuron. This increases the concentration of these neurotransmitters in the synaptic cleft, enhancing their signaling at postsynaptic receptors. The triple reuptake inhibition mechanism is thought to contribute to the compound's efficacy in improving attention and reducing impulsivity and hyperactivity.
|
|---|---|
| ln Vitro |
In clonal cell lines transfected with human transporters, centanafadine (EB-1020) predominantly inhibits monoamine reuptake; its IC50 values for NE and DA transporters, respectively, are 6 and 38 nM. On 5-HT transporters, centanafadine has less of an impact. Little as a result of its inhibition of monoamine reuptake. The IC50 value for 5-HT is 83 nM [1].
In vitro, centanafadine has been shown to potently inhibit DAT, NET, and SERT with IC50 values in the nanomolar range. The compound exhibits balanced inhibition of all three transporters, with a profile that distinguishes it from other ADHD medications. In cellular assays, centanafadine increases the accumulation of dopamine, norepinephrine, and serotonin in the synaptic cleft, as measured by neurotransmitter uptake inhibition assays. |
| ln Vivo |
Centanafadine dramatically raised the levels of NE and DA concentration in the rat prefrontal cortex in vivo in microdialysis tests. The highest effect was seen for NE, with peak increases of 375% and 300%, respectively. Additionally, centanafadine enhanced the extracellular levels of DA in the striatum. To 400% of the baseline, the concentration was raised. Based on behavioral tests, centanafadine does not promote locomotor activity in adult rats within the optimal dose range, and it dose-dependently reduces immobility in mice to 13% of control levels in the depressed tail-suspension test. In neonatal rats harmed by the neurotoxin 6-hydroxydopamine (100 μg intracisternally), centanafadine dose-dependently decreases locomotor hyperactivity; this is a well-established animal model of attention deficit hyperactivity disorder (ADHD) [1].
In vivo, centanafadine has demonstrated efficacy in preclinical models of ADHD and has been evaluated in clinical trials for the treatment of ADHD. In animal models, the compound has been shown to improve attention, reduce impulsivity, and decrease hyperactivity. Clinical trials have shown that centanafadine significantly reduces ADHD symptoms in children, adolescents, and adults, with a favorable safety and tolerability profile. |
| Enzyme Assay |
Centanafadine's activity can be assessed using in vitro neurotransmitter uptake inhibition assays. These assays measure the compound's ability to inhibit the uptake of radiolabeled dopamine, norepinephrine, or serotonin into cells expressing the respective transporters. IC50 values are determined from dose-response curves. The compound's binding affinity to DAT, NET, and SERT can be evaluated using radioligand binding assays.
|
| Cell Assay |
Cellular assays for centanafadine involve using cells that express DAT, NET, or SERT to measure neurotransmitter uptake inhibition. Cells are incubated with the compound and radiolabeled neurotransmitter, and the amount of neurotransmitter taken up into the cells is measured. Inhibition of uptake is calculated relative to control. The compound's effects on neurotransmitter levels in neuronal cultures can also be assessed.
|
| Animal Protocol |
In vivo animal model protocols for centanafadine involve its administration (typically orally) to animal models of ADHD, such as the spontaneously hypertensive rat (SHR) or the 6-hydroxydopamine (6-OHDA) lesioned rat. Behavioral tests assessing attention, impulsivity, and hyperactivity are performed, including the five-choice serial reaction time task (5-CSRTT) and the open field test. Pharmacokinetic studies are also conducted to assess the compound's exposure and brain penetration.
|
| ADME/Pharmacokinetics |
Centanafadine is an orally active compound with favorable pharmacokinetic properties. It is well-absorbed after oral administration and has a half-life that supports twice-daily or once-daily dosing. The compound is metabolized in the liver, primarily by CYP2D6, and its metabolites are excreted in the urine. Pharmacokinetic data from clinical trials have shown dose-proportional exposure and moderate inter-patient variability.
|
| Toxicity/Toxicokinetics |
Centanafadine has a favorable safety and tolerability profile in clinical trials. Common adverse effects include gastrointestinal disturbances (nausea, vomiting, decreased appetite), headache, and insomnia. As a triple reuptake inhibitor, it has the potential for drug interactions with monoamine oxidase inhibitors (MAOIs) and other serotonergic agents. The compound is not associated with significant cardiovascular effects at therapeutic doses.
|
| References | |
| Additional Infomation |
Centanafadine HCl (CAS# 923981-14-0) is the hydrochloride salt form of centanafadine, a triple reuptake inhibitor targeting dopamine, norepinephrine, and serotonin transporters. It has been developed for the treatment of attention-deficit/hyperactivity disorder (ADHD). Centanafadine increases the levels of dopamine, norepinephrine, and serotonin in the synaptic cleft, enhancing neurotransmission in brain regions involved in attention and impulse control. It has shown efficacy in clinical trials for ADHD.
|
| Molecular Formula |
C15H16CLN
|
|---|---|
| Molecular Weight |
245.747242927551
|
| Exact Mass |
245.097
|
| CAS # |
923981-14-0
|
| Related CAS # |
Centanafadine;924012-43-1
|
| PubChem CID |
68943792
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
1
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
17
|
| Complexity |
287
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
C1[C@H]2[C@@]1(CNC2)C3=CC4=CC=CC=C4C=C3.Cl
|
| InChi Key |
ACVMJAJGCQUPKX-LIOBNPLQSA-N
|
| InChi Code |
InChI=1S/C15H15N.ClH/c1-2-4-12-7-13(6-5-11(12)3-1)15-8-14(15)9-16-10-15;/h1-7,14,16H,8-10H2;1H/t14-,15+;/m1./s1
|
| Chemical Name |
(1R,5S)-1-naphthalen-2-yl-3-azabicyclo[3.1.0]hexane;hydrochloride
|
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : ~125 mg/mL (~508.65 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (8.46 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 (8.46 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 20.8 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: ≥ 2.08 mg/mL (8.46 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 | 4.0692 mL | 20.3459 mL | 40.6918 mL | |
| 5 mM | 0.8138 mL | 4.0692 mL | 8.1384 mL | |
| 10 mM | 0.4069 mL | 2.0346 mL | 4.0692 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
