SKF-83566 is a potent, BBB (blood-brain barrier) permeable (penetrable), orally bioactive D1-like dopamine receptor antagonist. It can also work as a weaker competitive antagonist. On 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 in research to study PD/Parkinson's disease and the relief of nicotine cravings.

Physicochemical Properties

Molecular Formula	C17H18BRNO
Molecular Weight	332.23
Exact Mass	367.034
CAS #	99295-33-7
Related CAS #	SKF-83566 hydrobromide;108179-91-5
PubChem CID	1243
Appearance	Off-white to light yellow solid powder
Boiling Point	447.5ºC at 760mmHg
Flash Point	224.4ºC
LogP	4.514
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	1
Heavy Atom Count	20
Complexity	318
Defined Atom Stereocenter Count	0
InChi Key	XFTVOHWWEQGXLS-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H18BrNO/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
Chemical Name	8-bromo-3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol
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	When single-pulse stimulation is applied, SKF-83566 (0.1 μM–10 μM) increases peak evoked extracellular DA concentration ([DA]o) in a concentration-dependent manner. Peak increases of up to 65% are observed when 5 μM is applied. For this effect, SKF-83566 has an EC50 value of 1.3 μM[2]. The [3H]DA uptake is inhibited by SKF-83566, with an IC50 of 5.73 μM. Moreover, tests on [3H]DA uptake and [3H]CFT binding show that SKF-83566 inhibits [3H]CFT binding more successfully, with an IC50 of 0.51 μM [2]. Likewise, with an IC50 of 0.77 μM, SKF-83566 also prevented [3H]CFT binding in LLc-PK-rDAT cell membrane preparations [2].
ln Vivo	SKF 83566 (oral; 20 μg/mL; 7 days) did not change LTP (115%) in any way. SKF 83566 + nicotine + cocaine, 120%; nicotine + cocaine, 143%), however, significantly inhibited the increase of long-term synaptic potentiation (LTP) caused by nicotine pretreatment[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.
Additional Infomation	8-bromo-3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol is a benzazepine.

Solubility Data

Solubility (In Vitro)

DMSO: 33.33 mg/mL (100.32 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.52 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 25.0 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: ≥ 2.5 mg/mL (7.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (7.52 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 25.0 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	3.0100 mL	15.0498 mL	30.0996 mL
	5 mM	0.6020 mL	3.0100 mL	6.0199 mL
	10 mM	0.3010 mL	1.5050 mL	3.0100 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.