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.

Physicochemical Properties

Molecular Formula	C16H16CL3N
Molecular Weight	328.6639
Exact Mass	327.034
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	SEP225289SEP-225,289 DasotralineSEP225,289 SEP225289 Dasotraline HCl SEP225,289 SEP-225289Dasotraline 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)

Biological Activity

Targets	IC50: 4 nM (dopamine), 6 nM (norepinephrine), 11 nM (serotonin)[1]
ln Vivo	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].
References	[1]. Characterization of the electrophysiological properties of triple reuptake inhibitors on monoaminergic neurons. Int J Neuropsychopharmacol. 2011 Mar;14(2):211-23. [2]. SEP-225289 serotonin and dopamine transporter occupancy: a PET study.

Solubility Data

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 (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	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.