SKF-83566 HBr is a potent, BBB (blood-brain barrier) permeable (penetrable), orally bioactive D1-like dopamine receptor antagonist, which can also work as a weaker competitive antagonist. At vascular 5-HT2 receptors (Ki = 11 nM). SKF-83566 is a competitive dopamine transporter (DAT) inhibitor (antagonist) with IC50 of 5.7 μM. In isolated rabbit thoracic aorta, SKF-83566 is more selective for adenylyl cyclase 2 (AC2) than AC1 and AC5. SKF-83566 may be used to study PD/Parkinson's disease and the relief of nicotine cravings.

Physicochemical Properties

Molecular Formula	C17H19BR2NO
Molecular Weight	413.15
Exact Mass	410.983
CAS #	108179-91-5
Related CAS #	SKF-83566;99295-33-7
PubChem CID	23581817
Appearance	Typically exists as solid at room temperature
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	1
Heavy Atom Count	21
Complexity	318
Defined Atom Stereocenter Count	0
SMILES	BrC1=C(C([H])=C2C(=C1[H])C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C2([H])C1C([H])=C([H])C([H])=C([H])C=1[H])O[H].Br[H]
InChi Key	SDQJYYGODYRPBR-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H18BrNO.BrH/c1-19-8-7-13-9-16(18)17(20)10-14(13)15(11-19)12-5-3-2-4-6-12;/h2-6,9-10,15,20H,7-8,11H2,1H3;1H
Chemical Name	8-bromo-3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol;hydrobromide
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

Targets	D1 Receptor D5 Receptor 5-HT2 Receptor 11 nM (Ki)
ln Vitro	Peak evoked extracellular DA concentration ([DA]o) elicited by single-pulse stimulation increases concentration-dependently with SKF-83566 (0.1 μM–10 μM), reaching a maximum 65% rise with 5 μM. SKF-83566's EC50 value for this effect is 1.3 μM[2]. At 5.73 μM, SKF-83566 reduced the absorption of [3H]DA. Furthermore, in investigations on [3H]DA uptake and [3H]CFT binding, SKF-83566 more effectively inhibits the binding of [3H]CFT, a cocaine analog, with an IC50 of 0.51 μM. Similarly, in LLc-PK-rDAT cell preparations, SKF-83566 likewise suppresses [3H]CFT binding, with an IC50 of 0.77 μM[2].
ln Vivo	LTP (115%) is not affected by SKF 83566 hydrobromide (oral treatment; 20 µg/mL; 7 days). The augmentation of long-term synaptic potentiation (LTP) brought on by nicotine pretreatment is, however, strongly blocked by the combination of SKF 83566 and nicotine (SKF 83566+nicotine+cocaine, 120%; nicotine+cocaine, 143%)[1].
Animal Protocol	Animal/Disease Models: Male C57BL6/J mice (6- to 9-wk-old)[1] Doses: 20 µg /mL (Together with nicotine for 7 d, followed by the injection of cocaine) Route of Administration: Oral administration; 7 days Experimental Results: Blocked nicotine and cocaine-induced facilitation of LTP.
References	[1]. D1/D5 Receptors and Histone Deacetylation Mediate the Gateway Effect of LTP in Hippocampal Dentate Gyrus. [2]. SKF-83566, a D1-dopamine Receptor Antagonist, Inhibits the Dopamine Transporter. J Neurochem. 2011 Sep;118(5):714-20. [3]. SCH 23390 and SK&F 83566 are antagonists at vascular dopamine and serotonin receptors. Eur J Pharmacol. 1985 Jan 22;108(2):205-8. [4]. Development of a high-throughput screening paradigm for the discovery of small-molecule modulators of adenylyl cyclase: identification of an adenylyl cyclase 2 inhibitor. J Pharmacol Exp Ther. 2013 Nov;347(2):276-87. [5]. D1/D5 receptors and histone deacetylation mediate the Gateway Effect of LTP in hippocampal dentate gyrus. Learn Mem. 2014 Feb 18;21(3):153-60. doi: 10.1101/lm.032292.113.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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	2.4204 mL	12.1021 mL	24.2043 mL
	5 mM	0.4841 mL	2.4204 mL	4.8409 mL
	10 mM	0.2420 mL	1.2102 mL	2.4204 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.