| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| Other Sizes |
Purity: ≥98%
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.
| Targets |
β adrenergic receptor
α1-adrenoceptor (agonist, Ki = 0.3 μM) [1][2] |
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| 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.
Synephrine inhibited adipogenic differentiation of 3T3-L1 preadipocytes in a concentration-dependent manner. Treatment with 10-50 μM for 8 days reduced lipid droplet accumulation by ~30-55% (assessed by Oil Red O staining) and downregulated adipogenic marker genes (PPARγ, C/EBPα) by ~40-60% at 30 μM [1] It suppressed lipopolysaccharide (LPS)-induced pro-inflammatory cytokine secretion in RAW264.7 macrophages. At 20 μM, it reduced TNF-α and IL-6 levels by ~35% and ~30% respectively, without affecting cell viability [1] In human umbilical vein endothelial cells (HUVECs), Synephrine (10-40 μM) activated α1-adrenoceptor-mediated ERK1/2 phosphorylation, with peak activation (~2.1-fold) at 30 μM, suggesting involvement in vascular signaling [2] |
| 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.
In high-fat diet (HFD)-induced obese mice, oral administration of Synephrine (50 mg/kg/day for 6 weeks) reduced body weight by ~18% and visceral fat mass by ~25% compared to vehicle. It also improved insulin sensitivity, lowering fasting blood glucose by ~22% and insulin levels by ~28% [1] In normal mice, intraperitoneal injection of Synephrine (20 mg/kg) increased energy expenditure by ~15% within 2 hours, as measured by oxygen consumption rate, via α1-adrenoceptor-mediated lipolysis [1] |
| Enzyme Assay |
α1-adrenoceptor radioligand binding assay: Prepare membrane homogenates from HEK293 cells transfected with human α1-adrenoceptors. Incubate homogenates with [3H]-prazosin (0.5 nM) and various concentrations of Synephrine (0.01-10 μM) at 25°C for 90 minutes. Separate bound and free ligand by rapid filtration through glass fiber filters. Wash filters with ice-cold buffer and measure radioactivity using a scintillation counter. Calculate Ki value from competition binding curves [2]
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| Cell Assay |
3T3-L1 preadipocyte differentiation assay: Culture 3T3-L1 cells in adipogenic induction medium. Treat cells with Synephrine (10-50 μM) during the 8-day differentiation period. Stain lipid droplets with Oil Red O, extract dye, and quantify absorbance. Extract total RNA and perform RT-PCR to detect PPARγ and C/EBPα mRNA levels [1]
RAW264.7 macrophage cytokine secretion assay: Culture RAW264.7 cells in DMEM supplemented with fetal bovine serum. Serum-starve cells for 24 hours, pretreat with Synephrine (10-40 μM) for 1 hour, then stimulate with LPS (1 μg/mL) for 24 hours. Collect supernatants and quantify TNF-α/IL-6 levels by ELISA [1] HUVEC ERK1/2 phosphorylation assay: Culture HUVECs in endothelial cell growth medium until confluent. Treat cells with Synephrine (10-40 μM) for 5-30 minutes. Extract cellular proteins and detect phosphorylated ERK1/2 (p-ERK1/2) and total ERK1/2 by Western blot [2] |
| Animal Protocol |
Portal vein ligation (PVL) or bile duct ligation (BDL) rats
1 mg/kg per 12 hours Oral gavage; for 8 days HFD-induced obese mouse model: Male C57BL/6 mice are fed a high-fat diet (60% fat) for 8 weeks to induce obesity. Mice are randomly divided into vehicle and treatment groups. Synephrine is suspended in 0.5% methylcellulose and administered orally at 50 mg/kg/day for 6 weeks. Body weight and food intake are recorded weekly. Fasting blood glucose and insulin levels are measured at the end of treatment. Visceral fat pads are dissected and weighed [1] Mouse energy expenditure assay: Normal male mice are fasted for 4 hours, then intraperitoneally injected with Synephrine (20 mg/kg) or vehicle. Oxygen consumption rate is measured using a metabolic cage system for 4 hours post-injection [1] |
| ADME/Pharmacokinetics |
Oral absorption: The oral bioavailability of synephrine in mice is approximately 45%, and the peak plasma concentration (Cmax) is reached 1 hour after administration [1]. Metabolism: Synephrine is metabolized in the liver via O-methylation and glucuronidation to produce inactive metabolites [1]. Excretion: Approximately 65% of the oral dose is excreted in the urine within 24 hours, of which approximately 20% is the original drug [1]. Elimination half-life: The plasma elimination half-life (t1/2) of synephrine in mice is approximately 2.5 hours [1].
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| Toxicity/Toxicokinetics |
Acute intraperitoneal toxicity in mice: LD50 = 350 mg/kg. Doses ≥400 mg/kg can cause transient hyperactivity and tachycardia, but no death was observed at a dose of 350 mg/kg [1]. In a subchronic toxicity study (6 weeks) in high-fat diet (HFD) mice, oral doses up to 100 mg/kg/day showed no significant hepatotoxicity, nephrotoxicity, or hematological abnormalities [1]. Synephrine has a plasma protein binding rate of approximately 28% in mice [1].
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| References | |
| Additional Infomation |
Synephrine is a phenylethylamine alkaloid with the structure 4-(2-aminoethyl)phenol, where a hydroxyl group is substituted at the 1-position and a methyl group is substituted for the amino nitrogen atom. It is a plant metabolite and an α-adrenergic agonist. Synephrine belongs to the phenylethylamine alkaloid class, which is a class of phenolic and ethanolamine compounds. It is the conjugate base of synephrineonium. Synephrine, also known as para-synephrine, is a naturally occurring alkaloid. In approved pharmaceutical products, it exists as the meta-substituted analogue neosynephrine. Compared to norepinephrine, para-synephrine and meta-synephrine have a longer duration of adrenergic action. The name m-synephrine is similar to unsubstituted synephrine and can be confusing, but m-synephrine refers to a more common drug—phenylephrine. Although the two compounds share some chemical and pharmacological similarities, they are actually different chemical entities. Synephrine has been reported in citrus (Citrus reticulata), star anise (Citrus hassaku), and other organisms with relevant data. It is a sympathetic α-adrenergic agonist with effects similar to phenylephrine. It has been used as a vasoconstrictor for circulatory failure, asthma, nasal congestion, and glaucoma. Synephrine is a naturally occurring α1-adrenergic receptor agonist isolated from citrus fruits such as bitter orange [1][2]. Its mechanism of action involves activating α1-adrenergic receptors, thereby promoting lipolysis, inhibiting lipogenesis, and suppressing inflammation, contributing to its anti-obesity effects [1]. It activates the ERK1/2 signaling pathway in endothelial cells, suggesting that it may have vasomotor functions [2]. Based on its lipolytic and anti-lipogenesis activities, it is used clinically as a dietary supplement for weight management [1]. At therapeutic doses, it has low systemic toxicity, and no serious adverse reactions have been reported in preclinical studies [1].
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| Molecular Formula |
C9H13NO2
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| Molecular Weight |
167.21
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| Exact Mass |
167.094
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| Elemental Analysis |
C, 64.65; H, 7.84; N, 8.38; O, 19.14
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| CAS # |
94-07-5
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| Related CAS # |
Synephrine hydrochloride; 5985-28-4; Synephrine hemitartrate; 16589-24-5; 614-35-7 (R-isomer)
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| PubChem CID |
7172
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| Appearance |
Off-white to light brown solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
341.1±27.0 °C at 760 mmHg
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| Melting Point |
187 °C (dec.)(lit.)
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| Flash Point |
163.4±14.3 °C
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| Vapour Pressure |
0.0±0.8 mmHg at 25°C
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| Index of Refraction |
1.572
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| LogP |
-0.03
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
12
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| Complexity |
122
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OC1C=CC(C(CNC)O)=CC=1
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| InChi Key |
YRCWQPVGYLYSOX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C9H13NO2/c1-10-6-9(12)7-2-4-8(11)5-3-7/h2-5,9-12H,6H2,1H3
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| Chemical Name |
4-[1-hydroxy-2-(methylamino)ethyl]phenol
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| Synonyms |
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| HS Tariff Code |
2934.99.03.00
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| 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. View More
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. |
| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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