Synephrine [Synephrine (+/-); (+/-)-Synephrine; Oxedrine], a naturally occurring protoalkaloid found in and extracted from bitter orange and other citrus species, is commonly used for weight loss. Ephedrine has been substituted with synephrine. Adverse cardiovascular reactions are suspected in products containing synephrine or bitter orange. In L6 skeletal muscle cells, synephrine can promote glucose consumption (Glut4-dependent glucose uptake) by upregulating AMPK activity, independent of insulin-stimulated PI3 kinase-Akt activity.

Physicochemical Properties

Molecular Formula	C9H13NO2
Molecular Weight	167.21
Exact Mass	167.094
Elemental Analysis	C, 64.65; H, 7.84; N, 8.38; O, 19.14
CAS #	94-07-5
Related CAS #	Synephrine hydrochloride; 5985-28-4; Synephrine hemitartrate; 16589-24-5; 614-35-7 (R-isomer)
PubChem CID	7172
Appearance	Off-white to light brown solid powder
Density	1.2±0.1 g/cm3
Boiling Point	341.1±27.0 °C at 760 mmHg
Melting Point	187 °C (dec.)(lit.)
Flash Point	163.4±14.3 °C
Vapour Pressure	0.0±0.8 mmHg at 25°C
Index of Refraction	1.572
LogP	-0.03
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	3
Heavy Atom Count	12
Complexity	122
Defined Atom Stereocenter Count	0
SMILES	OC1C=CC(C(CNC)O)=CC=1
InChi Key	YRCWQPVGYLYSOX-UHFFFAOYSA-N
InChi Code	InChI=1S/C9H13NO2/c1-10-6-9(12)7-2-4-8(11)5-3-7/h2-5,9-12H,6H2,1H3
Chemical Name	4-[1-hydroxy-2-(methylamino)ethyl]phenol
Synonyms	Oxedrine; Synephrine (racemate); Synephrine (+/-); (+/-)-Synephrine
HS Tariff Code	2934.99.03.00
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	β adrenergic receptor
ln Vitro	In vitro activity: Synephrine is a substance that is frequently used to reduce weight. Synephrine has become a highly sought-after substitute for 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.
ln Vivo	Synephrine (1 mg/kg; oral gavage; for 8 days; PVL and BDL rats) significantly reduces the hyperdynamic state in both PVL and BDL rats. Synephrine treatment results in significant reductions in portal venous pressure, portal tributary blood flow, and cardiac index in PVL and BDL rats, but increases in mean arterial pressure, systemic vascular resistance, and portal territory vascular resistance.
Animal Protocol	Portal vein ligation (PVL) or bile duct ligation (BDL) rats 1 mg/kg per 12 hours Oral gavage; for 8 days
References	[1]. Int J Med Sci . 2012;9(7):527-38. [2]. Biochem Biophys Res Commun . 2012 Feb 24;418(4):720-4.
Additional Infomation	Synephrine is a phenethylamine alkaloid that is 4-(2-aminoethyl)phenol substituted by a hydroxy group at position 1 and a methyl group at the amino nitrogen. It has a role as a plant metabolite and an alpha-adrenergic agonist. It is a phenethylamine alkaloid, a member of phenols and a member of ethanolamines. It is a conjugate base of a synephrinium. Synephrine, also referred to as, p-synephrine, is naturally occurring alkaloid. It is present in approved drug products as neo-synephrine, its m-substituted analog. p-synephrine and m-synephrine are known for their longer acting adrenergic effects compared to norepinephrine. The similarity of naming between m-synephrine and the unsubstituted form, synephrine, is a source of some confusion however m-synephrine refers to a related drug more commonly known as phenylephrine. While the compounds share some chemical and pharmacological similarities, they are in fact distinct chemical entities. Synephrine has been reported in Citrus reticulata, Citrus hassaku, and other organisms with data available. Sympathetic alpha-adrenergic agonist with actions like PHENYLEPHRINE. It is used as a vasoconstrictor in circulatory failure, asthma, nasal congestion, and glaucoma.

Solubility Data

Solubility (In Vitro)

DMSO: 33~83.3 mg/mL (197.3~498.4 mM) Water: <1 mg/mL Ethanol: ~2 mg/mL (~12 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (12.44 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 (12.44 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 20.8 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: ≥ 2.08 mg/mL (12.44 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	5.9805 mL	29.9025 mL	59.8050 mL
	5 mM	1.1961 mL	5.9805 mL	11.9610 mL
	10 mM	0.5981 mL	2.9903 mL	5.9805 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.