| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| 500mg | |||
| Other Sizes |
Purity: ≥98%
Dasotraline (formerly known as SEP-225289; SEP-225,289) is a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI) with anti-depressant and anti-ADHD activity. The drug is no longer being developed for major depressive disorder (MDD), but is still under investigation for the treatment of attention-deficit hyperactivity disorder (ADHD) and eating disorders.
Dasotraline (development code SEP-225289; (1R,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-amine) is a novel inhibitor of dopamine and norepinephrine reuptake that has completed pivotal clinical studies for the treatment of attention-deficit/hyperactivity disorder (ADHD) and binge eating disorder (BED). Structurally, dasotraline is a stereoisomer of desmethylsertraline, the active metabolite of the antidepressant sertraline. Unlike current ADHD medications that provide rapid but short-lived effects, dasotraline is characterized by slow absorption and prolonged elimination, providing stable plasma concentrations over a 24-hour dosing interval. Preclinical studies show that dasotraline preferentially inhibits dopamine transporter and norepinephrine transporter relative to serotonin transporter, making it a dual reuptake inhibitor with a unique pharmacokinetic profile.| Targets |
Dasotraline primarily targets the dopamine transporter (DAT, IC50 = 3 nM, human) and the norepinephrine transporter (NET, IC50 = 4 nM, human), functioning as a preferential dual reuptake inhibitor. It also inhibits the serotonin transporter (SERT, IC50 = 15 nM, human) but with weaker potency. The compound achieves 50% transporter occupancy at plasma concentrations (TO50) of 32 ng/mL for DAT, 109 ng/mL for NET, and 276 ng/mL for SERT in mouse ex vivo occupancy studies
IC50: 4 nM (dopamine), 6 nM (norepinephrine), 11 nM (serotonin)[1] |
|---|---|
| ln Vitro |
In vitro radiometric functional uptake studies demonstrated that dasotraline is a potent inhibitor of human dopamine transporter (hDAT) with an IC50 of 3 nM and human norepinephrine transporter (hNET) with an IC50 of 4 nM. The compound shows approximately 5-fold weaker inhibition of human serotonin transporter (hSERT) with an IC50 of 15 nM. This preferential inhibition profile distinguishes dasotraline from non-selective triple reuptake inhibitors. The compound has a molecular weight of 292.2, a logP of 4.3, and a topological polar surface area consistent with CNS penetration.
|
| ln Vivo |
In mouse ex vivo occupancy studies, dasotraline demonstrated total plasma concentration-dependent occupancy at DAT, NET, and SERT, with TO50 (50% transporter occupancy) values of 32, 109, and 276 ng/mL, respectively. In SPECT imaging studies in baboons, intravenous administration of dasotraline (0.2 mg/kg) displaced radiotracer binding to DAT by 87%, but only 20% at NET and SERT, confirming in vivo preferential DAT occupancy. In rat microdialysis studies performed in prefrontal cortex and striatum, dasotraline produced sustained (>4 hours) increases in dopamine and norepinephrine concentrations. The compound was also more potent at increasing synaptic dopamine in the striatum and norepinephrine in the prefrontal cortex than serotonin in these regions.
Dasotraline administered acutely dose-dependently inhibits the spontaneous firing rate of LC NE, VTA DA, and DR 5-HT neurons via activating their respective α2, D2, and 5-HT1A autoreceptors. Dasotraline only somewhat reduces VTA DA and DR 5-HT neuronal discharge, however it primarily suppresses the firing rate of LC NE neurons. Since SEP-225289 extends the time required for a 50% recovery of the firing activity of dorsal hippocampal CA3 pyramidal neurons from the inhibition generated by microiontophoretic administration of 5-HT and NE, it is equipotent at blocking 5-HT and NE transporters[1]. As SEP-225289 dosage increases, average dopamine and serotonin transporter occupancies rise as well. The average occupancies of dopamine and serotonin transporters are 33%±11% and 2%±13% for 8 mg, 44%±4% and 9%±10% for 12 mg, and 49%±7% and 14%±15% for 16 mg, respectively[2]. |
| Enzyme Assay |
Radiometric functional uptake studies were used to evaluate dasotraline's inhibitory potency at human DAT, NET, and SERT. The assay involves measuring the uptake of radiolabeled neurotransmitters (e.g., [³H]dopamine for DAT, [³H]norepinephrine for NET, [³H]serotonin for SERT) into cells expressing the respective human transporters. IC50 values are determined by measuring inhibition of uptake at various compound concentrations and fitting data to a sigmoidal concentration-response curve.
|
| Cell Assay |
Cell-based assays for dasotraline utilize cell lines expressing human DAT, NET, or SERT (e.g., HEK-293 or CHO cells stably transfected with the respective transporter cDNA). Cells are incubated with varying concentrations of dasotraline and radiolabeled neurotransmitter substrates. After a specified incubation period, the reaction is terminated, and accumulated radioactivity is measured by liquid scintillation counting to calculate percent inhibition and determine IC50 values.
|
| Animal Protocol |
Mouse ex vivo occupancy study: Mice are administered dasotraline at various doses, and plasma samples are collected at specified time points. Brain tissue is harvested, and transporter occupancy is measured using radiolabeled tracers specific for DAT, NET, and SERT. TO50 values (plasma concentration producing 50% transporter occupancy) are calculated. Rat microdialysis study: Rats are implanted with microdialysis probes in the prefrontal cortex and striatum. Dasotraline is administered (route and dose as specified), and dialysate samples are collected at regular intervals. Dopamine, norepinephrine, and serotonin concentrations are analyzed by HPLC with electrochemical detection to assess neurotransmitter changes over time.
|
| ADME/Pharmacokinetics |
Dasotraline has a unique pharmacokinetic profile characterized by slow absorption (Tmax ~10-12 hours) and prolonged elimination. Following oral administration, the mean apparent half-life is approximately 47 hours in the ADHD population (range 47-77 hours across dose cohorts), supporting once-daily dosing. Exposure increases nearly dose-proportionally; a 4-fold higher dose results in 4.2- to 5.6-fold increases in Cmax and AUC. Following multiple daily doses, dasotraline exposure accumulates 8- to 11-fold over 21 days, reaching steady-state by approximately 10 days of dosing. In a phase I study with 8 mg single dose, Cmax was 2.02 ng/mL (18.4% CV) with median Tmax of 10 hours, and mean half-life was 61.3 hours (34.2% CV). Apparent clearance (CL/F) was 32.3 L/h, and volume of distribution (Vz/F) was 2860 L. Dasotraline is extensively metabolized, primarily by CYP2B6 (63% of metabolism), with contributions from CYP2D6 (12%), CYP2C19 (11%), and CYP3A4/5 (14%). CYP2B6 autoinhibition contributes to drug accumulation at steady state. The compound is not a CYP inducer but inhibits CYP2B6, CYP2C19, CYP2D6, and CYP3A4/5.
|
| Toxicity/Toxicokinetics |
In clinical trials for ADHD, dasotraline was generally well-tolerated. The most common adverse events included decreased appetite (showing dose dependence) and insomnia. In the pivotal phase III trials, dasotraline 4 mg daily in children and 6 mg daily in adults demonstrated acceptable tolerability. A systematic review and meta-analysis of five clinical trials (total safety population of 1,523 patients) concluded that dasotraline improves ADHD symptoms with acceptable tolerability, though the incidence of decreased appetite was dose-dependent. No significant safety signals related to cardiovascular events, hepatotoxicity, or other serious adverse events were identified in the analyzed studies. The drug is contraindicated in patients receiving monoamine oxidase inhibitors (MAOIs). The unique slow absorption/elimination profile reduces the peak/trough fluctuations associated with stimulant medications, which may contribute to its tolerability.
|
| References | |
| Additional Infomation |
Dasotraline (UNII: 4D28EY0L5T; CAS: 675126-05-3) has the molecular formula C₁₆H₁₅Cl₂N and a molecular weight of 292.2. The IUPAC name is (1R,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-amine. It is also known as (1R,4S)-trans-norsertraline and SEP-225289. Structurally, dasotraline is the (1R,4S) stereoisomer of desmethylsertraline, an active metabolite of the marketed SSRI antidepressant sertraline (Zoloft). Phase II and III clinical trials have demonstrated that dasotraline significantly reduces ADHD total symptom scores compared to placebo (SMD: -0.35; 95% CI: -0.55 to -0.15; P < 0.001), with significant improvements in both hyperactivity/impulsivity and inattentiveness subscales. In adults with ADHD, a 6 mg daily dose showed significant improvement, while in children aged 6-12 years, a 4 mg daily dose was effective. Dasotraline is also under investigation for binge eating disorder (BED), having completed Phase III studies. The unique pharmacokinetic profile (slow absorption/long half-life) provides stable 24-hour dopamine and norepinephrine reuptake inhibition, representing a novel pharmacological approach to ADHD management distinct from both short-acting stimulants and longer-acting non-stimulants. Population pharmacokinetic modeling indicates that body weight is a significant covariate for dasotraline exposure, but age, sex, race, and ethnicity were not significant predictors of variability.
|
| Molecular Formula |
C16H16CL3N
|
|---|---|
| Molecular Weight |
328.6639
|
| Exact Mass |
327.034
|
| Elemental Analysis |
C, 58.47; H, 4.91; Cl, 32.36; N, 4.26
|
| CAS # |
675126-08-6
|
| Related CAS # |
Dasotraline;675126-05-3
|
| PubChem CID |
25192248
|
| Appearance |
White to off-white solid powder
|
| LogP |
6.421
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
1
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
20
|
| Complexity |
309
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
C1C[C@H](C2=CC=CC=C2[C@@H]1C3=CC(=C(C=C3)Cl)Cl)N.Cl
|
| InChi Key |
YKXHIERZIRLOLD-DFIJPDEKSA-N
|
| InChi Code |
InChI=1S/C16H15Cl2N.ClH/c17-14-7-5-10(9-15(14)18)11-6-8-16(19)13-4-2-1-3-12(11)13/h1-5,7,9,11,16H,6,8,19H21H/t11-,16+/m0./s1
|
| Chemical Name |
(1R,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-amine hydrochloride
|
| Synonyms |
SEP225289 HCl; SEP-225,289 HCl; Dasotraline; SEP225,289 HCl; SEP225289; Dasotraline HCl; SEP225,289; SEP-225289; Dasotraline 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 : ≥ 31 mg/mL (~94.32 mM)
H2O : ~1.61 mg/mL (~4.90 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0427 mL | 15.2133 mL | 30.4266 mL | |
| 5 mM | 0.6085 mL | 3.0427 mL | 6.0853 mL | |
| 10 mM | 0.3043 mL | 1.5213 mL | 3.0427 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02457819 | Completed | Drug:Dasotraline | Attention Deficit Hyperactivity Disorder | Sumitomo Pharma America,Inc. | June 30, 2015 | Phase 3 |
| NCT02564588 | Completed | Drug:Dasotraline Drug:Placebo |
Binge Eating Disorder | Sumitomo Pharma America,Inc. | October 2015 | Phase 2 Phase 3 |
| NCT03107026 | Completed | Drug:dasotraline 4mg Drug:dasotraline 6mg Drug:Placebo |
Binge Eating Disorder | Sumitomo Pharma America,Inc. | March 31, 2017 | Phase 3 |
| NCT03231800 | Completed | Drug:dasotraline Drug:Placebo |
Attention-Deficit Hyperactivity Disorder(ADHD) |
Sumitomo Pharma America,Inc. | July 31, 2017 | Phase 3 |
| NCT02160262 | Completed | Drug:Dasotraline | Adult Attention Deficit Hyperactivity Disorder |
Sumitomo Pharma America,Inc. | June 2014 | Phase 3 |
|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
