DOV-216,303 (Free Base) is a potent triple inhibitor of serotonin, norepinephrine, and dopamine reuptake, with IC50s of 14 nM, 20 nM, and 78 nM for hSERT, hNET, and hDAT, respectively. In the olfactory bulbectomy rat model, it can increase the release of monoamines in the prefrontal cortex and have antidepressant effects.

Physicochemical Properties

Molecular Formula	C11H11NCL2
Molecular Weight	228.11774
Exact Mass	227.027
CAS #	66504-40-3
Related CAS #	Amitifadine hydrochloride;410074-74-7;DOV-216,303;86215-36-3
PubChem CID	9795276
Appearance	Colorless to light yellow ointment
LogP	3.183
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	1
Rotatable Bond Count	1
Heavy Atom Count	14
Complexity	245
Defined Atom Stereocenter Count	0
SMILES	C1=CC(=C(C=C1C23CC3CNC2)Cl)Cl
InChi Key	BSMNRYCSBFHEMQ-UHFFFAOYSA-N
InChi Code	InChI=1S/C11H11Cl2N/c12-9-2-1-7(3-10(9)13)11-4-8(11)5-14-6-11/h1-3,8,14H,4-6H2
Chemical Name	1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane
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	In OBX and Sham animals, acute administration of DOV-216,303 (20 mg/kg, i.p.) dramatically raises dopamine, norepinephrine, and serotonin levels [2]. In the medial prefrontal cortex of OBX and Sham mice, chronic administration of DOV 216,303 (20 mg/kg, i.p., for 17 days) raises extracellular concentrations of dopamine, norepinephrine, and serotonin and significantly increases extracellular baseline serum concentration [2].
Animal Protocol	Animal/Disease Models: Male Sprague Dawley rats weighing 290 to 350 grams at the time of OBX or sham surgery [2]. Doses: 20 mg/kg. Management: IP one time/day for 17 days. Experimental Results: Extracellular concentrations of dopamine, norepinephrine, and serotonin were increased in the medial prefrontal cortex of OBX and Sham animals, and extracellular baseline serotonin concentrations were Dramatically increased. Animal/Disease Models: Male Sprague Dawley rats weighing 290 to 350 grams at the time of OBX or sham surgery [2]. Doses: 20 mg/kg. Management: IP once. Experimental Results: Dopamine, norepinephrine, and serotonin levels were Dramatically increased in OBX and Sham animals.
References	[1]. Discovery of N-methyl-1-(1-phenylcyclohexyl)methanamine, a novel triple serotonin, norepinephrine, and dopamine reuptake inhibitor. Bioorg Med Chem Lett. 2011 Mar 1;21(5):1438-41. [2]. The putative antidepressant DOV 216,303, a triple reuptake inhibitor, increases monoamine release in the prefrontal cortex of olfactory bulbectomized rats. Eur J Pharmacol. 2010 May 10;633(1-3):55-61.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 125 mg/mL (~547.96 mM) Ethanol : ~100 mg/mL (~438.37 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (9.12 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 (9.12 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	4.3837 mL	21.9183 mL	43.8366 mL
	5 mM	0.8767 mL	4.3837 mL	8.7673 mL
	10 mM	0.4384 mL	2.1918 mL	4.3837 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.