Dasotraline is a triple reuptake inhibitor that blocks dopamine, norepinephrine, and serotonin transporters with IC50 of 4, 6, and 11 nM, respectively.
Physicochemical Properties
| Molecular Formula | C₁₆H₁₅CL₂N |
| Molecular Weight | 292.203 |
| Exact Mass | 291.058 |
| CAS # | 675126-05-3 |
| Related CAS # | Dasotraline hydrochloride;675126-08-6 |
| PubChem CID | 9947999 |
| Appearance | Typically exists as solid at room temperature |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 409.6±45.0 °C at 760 mmHg |
| Flash Point | 201.5±28.7 °C |
| Vapour Pressure | 0.0±1.0 mmHg at 25°C |
| Index of Refraction | 1.614 |
| LogP | 4.59 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 1 |
| Rotatable Bond Count | 1 |
| Heavy Atom Count | 19 |
| Complexity | 309 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | N[C@@H]1CC[C@@H](C2=CC=C(Cl)C(Cl)=C2)C3=CC=CC=C31 |
| 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 | SEP-225,289 SEP225,289 SEP225,289 SEP-225289 SEP225289 SEP225289 Dasotraline Dasotraline HCl 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 |
| 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
| ln Vivo | The goal of the current in vivo electrophysiological investigation was to ascertain how the triple reuptake inhibitor Dasotraline (SEP-225289) affected the activity of HT neurons in the locus coeruleus (LC) NE, ventral tegmental area (VTA) DA, and dorsal raphe (DR) 5-neuron. When given abruptly, dasotraline activates α2, D2, and 5-HT1A autoreceptors, respectively, reducing the spontaneous firing rate of LC NE, VTA DA, and DR 5-HT neurons in a dose-dependent manner. Dasotraline very slightly decreased the firing rate of VTA DA and DR 5-HT neurons, while it mostly suppressed the firing rate of LC NE neurons. Since dasotraline increases dorsal hippocampal CA3 pyramidal neuron firing activity to the same degree needed for 50% recovery from 5-HT microiontophoresis-induced inhibition time (RT50) and NE, it is similar to naloxetine in terms of blocking 5-HT and NE transporters. The suppression of hippocampal pyramidal neuron firing activity following the micro-iontophoretic injection of 5-HT and NE, both before to and during the acute intravenous administration of cumulative doses of dasotraline (1-8 mg), was used to calculate the recovery time (RT). RT50 value was used to evaluate. /Kilogram. Dasotraline (1 and 2 mg/kg) did not change the firing activity of CA3 pyramidal neurons, but at the maximum dose (8 mg/kg), there was a notable 50% reduction in firing activity. In rats treated with WAY100635, dasotraline (0.5-2 mg/kg iv) significantly increased the DR 5-HT firing rate. Rats pretreated with WAY100635 had a considerable increase in the number of single spikes and bursts when given dasotraline [1]. |
| References |
[1]. Characterization of the electrophysiological properties of triple reuptake inhibitors on monoaminergic neurons. Int J Neuropsychopharmacol. 2011 Mar;14(2):211-23. |
| Additional Infomation |
Dasotraline is a serotonin, norepinephrine and dopamine reuptake inhibitor (SNDRI) that is under investigation for the treatment of Binge Eating Disorder, Adult Attention Hyperactivity Disorder, Attention Deficit Hyperactivity Disorder, and Adult Attention Deficit Hyperactivity Disorder. Mechanism of Action Dasotraline has been shown in preclinical studies to be a potent and balanced reuptake inhibitor of serotonin, norepinephrine and dopamine (SNDRI). Serotonin, norepinephrine and dopamine are neurotransmitters associated with depression. There are currently no marketed treatments for depression that inhibit reuptake of all three neurotransmitters. |
Solubility Data
| Solubility (In Vitro) | DMSO : ≥ 31 mg/mL (~106.09 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 | 3.4223 mL | 17.1116 mL | 34.2231 mL | |
| 5 mM | 0.6845 mL | 3.4223 mL | 6.8446 mL | |
| 10 mM | 0.3422 mL | 1.7112 mL | 3.4223 mL |