Synephrine HCl (Sympatol; oxedrine), the hydrochloride salt of synephrine which is a naturally occuring protoalkaloid extracted from bitter orange and other citrus species, is commonly used for weight loss. Synephrine has also been widely used as an alternative to ephedrine. Products that contain synephrine or bitter orange may cause negative cardiovascular reactions. Regardless of insulin-stimulated PI3 kinase-Akt activity in L6 skeletal muscle cells, synephrine can promote glucose consumption (Glut4-dependent glucose uptake) by upregulating AMPK activity.

Physicochemical Properties

Molecular Formula	C9H14CLNO2
Molecular Weight	203.67
Exact Mass	203.071
Elemental Analysis	C, 53.08; H, 6.93; Cl, 17.41; N, 6.88; O, 15.71
CAS #	5985-28-4
Related CAS #	Synephrine; 94-07-5; Synephrine hemitartrate; 16589-24-5
PubChem CID	42609626
Appearance	White to off-white solid powder
Boiling Point	341.1ºC at 760 mmHg
Melting Point	147-150ºC
Flash Point	163.4ºC
LogP	1.837
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	3
Heavy Atom Count	13
Complexity	122
Defined Atom Stereocenter Count	0
SMILES	Cl[H].O([H])C([H])(C1C([H])=C([H])C(=C([H])C=1[H])O[H])C([H])([H])N([H])C([H])([H])[H]
InChi Key	COTCEGYSNTWJQV-UHFFFAOYSA-N
InChi Code	InChI=1S/C9H13NO2.ClH/c1-10-6-9(12)7-2-4-8(11)5-3-7;/h2-5,9-12H,6H2,1H3;1H
Chemical Name	4-[1-hydroxy-2-(methylamino)ethyl]phenol;hydrochloride
Synonyms	Sympatol; Synephrine HCl; oxedrine
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	β adrenergic receptor
ln Vitro	Synephrine (0.1-30 μM) exhibits strong vasoconstrictive effects on isolated rat aortas in a dose-dependent manner that is significantly inhibited by pretreatment with ketanserin, prazosin, and BRL15572, but not by pretreatment with SB216641 and propranolol. This suggests that synephrine acts via serotonergic 5-HT(1D) receptors, adrenergic alpha(1)-receptors, and adrenergic alpha(1)-receptors.[2] Synephrine is the only partial agonist of the α1A-AR subtype that is stably expressed in HEK 293 cells, with an EC50 of 4 µM and a maximal response at 100 µM equal to 55.3% of the L-phenylephrine maximum, despite the fact that the Ki values of Synephrine, 1R, 2S-norephedrine, and β-phenethylamine are the same for all three subtypes. Synephrine may function as an antagonist rather than an agonist of the pre-synaptic α(2A)- and α(2C)-AR subtypes found in nerve terminals, according to functional studies on the α2A- and α2C-AR subtypes that are stably expressed in CHO cells. However, synephrine's antagonist activity is less than its partial agonist potency.[3] In a dose-dependent manner, synephrine (~100 μM) treatment raises basal glucose consumption over the control by up to 50% without compromising the viability of L6 skeletal muscle cells. When basal or insulin-stimulated lactic acid production and glucose consumption are combined, synephrine dramatically increases both of these processes. In addition, synephrine-induced glucose consumption and the translocation of Glut4 from the cytoplasm to the plasma membrane are responsive to AMPK inhibition but not PI3 kinase inhibition. Synephrine treatment stimulates the phosphorylation of AMPK but not Akt.[4]
ln Vivo	Eight days of administration of Synephrine (1 mg/kg per 12 hours) significantly reduces the portal tributary blood flow, portal venous pressure, and cardiac index in both PVL and BDL rats, and improves the hyperdynamic state in portal hypertensive rats induced by either partial portal vein ligation (PVL) or bile duct ligation (BDL).[1]
Animal Protocol	Dissolved in 0.1 N HCl; 1 mg/kg per 12 hours; Oral gavage Male Sprague-Dawley rats with portal hypertension (with or without cirrhosis) induced by bile duct ligation or partial portal vein ligation
References	[1]. Jpn J Pharmacol . 2001 Feb;85(2):183-8. [2]. J Pharmacol Sci . 2009 Sep;111(1):73-81. [3]. Planta Med . 2010 Jul;76(10):981-6. [4]. Biochem Biophys Res Commun . 2012 Feb 24;418(4):720-4.

Solubility Data

Solubility (In Vitro)	DMSO: ~14 mg/mL (~68.7 mM) Water: ~41 mg/mL (~201.3 mM) Ethanol: ~4 mg/mL (~19.6 mM)
Solubility (In Vivo)	Saline: 30 mg/mL  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.9099 mL	24.5495 mL	49.0990 mL
	5 mM	0.9820 mL	4.9099 mL	9.8198 mL
	10 mM	0.4910 mL	2.4550 mL	4.9099 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.