Details
| Stereochemistry | RACEMIC |
| Molecular Formula | C9H13NO2 |
| Molecular Weight | 167.205 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CNCC(O)C1=CC=C(O)C=C1
InChI
InChIKey=YRCWQPVGYLYSOX-UHFFFAOYSA-N
InChI=1S/C9H13NO2/c1-10-6-9(12)7-2-4-8(11)5-3-7/h2-5,9-12H,6H2,1H3
| Molecular Formula | C9H13NO2 |
| Molecular Weight | 167.205 |
| Charge | 0 |
| Count |
|
| Stereochemistry | RACEMIC |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Optical Activity | ( + / - ) |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/21904645Curator's Comment: The description was created based on several sources, including
https://www.drugs.com/international/oxedrine.html | https://clinicaltrials.gov/ct2/show/NCT01423019 | https://www.ncbi.nlm.nih.gov/pubmed/20217639
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21904645
Curator's Comment: The description was created based on several sources, including
https://www.drugs.com/international/oxedrine.html | https://clinicaltrials.gov/ct2/show/NCT01423019 | https://www.ncbi.nlm.nih.gov/pubmed/20217639
Oxedrine (Sympatol, p-synephrine) is a naturally occurring alkaloid molecule first appeared in Europe towards the end of the 1920s being sold as a drug under the brand name Sympatol. Oxedrine was then being prescribed as a remedy for a number of respiratory conditions, which include asthma, whooping cough, colds, and hay fever. More recently, synephrine gained popularity as a weight loss aid and it has become a favored component in the more popular brands of weight loss supplement stacks. This popularity can be attributed in part to the ban imposed on ephedra, to which it shares similar mechanisms of action. Most, if not all of the synephrine being sold as a dietary supplement is extracted and synthesized from the Citrus aurantium plant, more commonly known as bitter orange. Just like ephedrine, synephrine has vasoconstrictive abilities, although at a lesser potency compared to ephedrine. There is no mention of synephrine in editions of Drill's Pharmacology in Medicine later than the 3rd, nor is there any reference to synephrine in the 2012 Physicians' Desk Reference, nor in the current FDA "Orange Book". One current reference source describes synephrine as a vasoconstrictor that has been given to hypotensive patients, orally or by injection, in doses of 20–100 mg.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL1075144 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25262941 |
6.6 µM [EC50] | ||
Target ID: CHEMBL229 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20217639 |
4.11 null [pKi] | ||
Target ID: CHEMBL1867 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20217639 |
4.44 null [pKi] | ||
Target ID: CHEMBL1916 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20217639 |
4.61 null [pKi] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Advantra Z Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1.75 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18341680/ |
21 mg single, oral dose: 21 mg route of administration: Oral experiment type: SINGLE co-administered: CAFFEINE |
OXEDRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1.86 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18341680/ |
21 mg single, oral dose: 21 mg route of administration: Oral experiment type: SINGLE co-administered: CAFFEINE |
OXEDRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
427.9 ng × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18341680/ |
21 mg single, oral dose: 21 mg route of administration: Oral experiment type: SINGLE co-administered: CAFFEINE |
OXEDRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
466.4 ng × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18341680/ |
21 mg single, oral dose: 21 mg route of administration: Oral experiment type: SINGLE co-administered: CAFFEINE |
OXEDRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2.56 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18341680/ |
21 mg single, oral dose: 21 mg route of administration: Oral experiment type: SINGLE co-administered: CAFFEINE |
OXEDRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
2.64 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18341680/ |
21 mg single, oral dose: 21 mg route of administration: Oral experiment type: SINGLE co-administered: CAFFEINE |
OXEDRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
100 mg single, oral Studied dose |
healthy, 22.3 ± 1.6 |
|
100 mg 1 times / day multiple, oral Studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: |
healthy, 27 Health Status: healthy Age Group: 27 Sex: F Sources: |
Disc. AE: Ventricular fibrillation... AEs leading to discontinuation/dose reduction: Ventricular fibrillation Sources: |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Ventricular fibrillation | Disc. AE | 100 mg 1 times / day multiple, oral Studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: |
healthy, 27 Health Status: healthy Age Group: 27 Sex: F Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Screening for in vivo (anti)estrogenic activity of ephedrine and p-synephrine and their natural sources Ephedra sinica Stapf. (Ephedraceae) and Citrus aurantium L. (Rutaceae) in rats. | 2009-01 |
|
| Effects of chemopreventive citrus phytochemicals on human P-glycoprotein and multidrug resistance protein 1. | 2008-12-14 |
|
| Synephrine content of juice from Satsuma mandarins (Citrus unshiu Marcovitch). | 2008-10-08 |
|
| Determination of ephedrine alkaloids in Ephedra natural products using HPLC on a pentafluorophenylpropyl stationary phase. | 2008-09-29 |
|
| Selectivity and potential interference from phenolic compounds in chemiluminescence methods for the determination of synephrine. | 2008-09-13 |
|
| Concentrations of p-synephrine in fruits and leaves of Citrus species (Rutaceae) and the acute toxicity testing of Citrus aurantium extract and p-synephrine. | 2008-08 |
|
| Citrus aurantium--beware of the bitter orange. | 2008-07 |
|
| Vasospasm and stroke attributable to ephedra-free xenadrine: case report. | 2008-07 |
|
| Sensitive determination of norepinephrine, synephrine, and isoproterenol by capillary electrophoresis with indirect electrochemiluminescence detection. | 2008-07 |
|
| Certification of standard reference materials containing bitter orange. | 2008-07 |
|
| Human pharmacology of a performance-enhancing dietary supplement under resting and exercise conditions. | 2008-06 |
|
| Coronary spasm and thrombosis in a bodybuilder using a nutritional supplement containing synephrine, octopamine, tyramine and caffeine. | 2008-05 |
|
| In vitro anticholinesterase activity of various alkaloids. | 2007-12-12 |
|
| Effects of ingesting JavaFit Energy Extreme functional coffee on aerobic and anaerobic fitness markers in recreationally-active coffee consumers. | 2007-12-08 |
|
| Lipolysis induced by segment wall extract from Satsuma mandarin orange (Citrus unshu Mark). | 2007-12 |
|
| Trace amine-associated receptor 1-Family archetype or iconoclast? | 2007-12 |
|
| Mass spectrometric determination of the predominant adrenergic protoalkaloids in bitter orange (Citrus aurantium). | 2007-11-28 |
|
| Simultaneous determination of flavonoid and alkaloid compounds in Citrus herbs by high-performance liquid chromatography-photodiode array detection-electrospray mass spectrometry. | 2007-10-01 |
|
| Temperature effects on the enantioselectivity of basic analytes in capillary EKC using sulfated beta-CDs as chiral selectors. | 2007-10 |
|
| Fast high-performance liquid chromatography analysis of phenethylamine alkaloids in Citrus natural products on a pentafluorophenylpropyl stationary phase. | 2007-09-21 |
|
| Determination of bitter orange alkaloids in dietary supplement Standard Reference Materials by liquid chromatography with atmospheric-pressure ionization mass spectrometry. | 2007-09 |
|
| Chromatographic and electrophoretic methods for the analysis of phenethylamine [corrected] alkaloids in Citrus aurantium. | 2007-08-17 |
|
| Influence of microemulsion chirality on chromatographic figures of merit in EKC: results with novel three-chiral-component microemulsions and comparison with one- and two-chiral-component microemulsions. | 2007-08 |
|
| Two-chiral component microemulsion EKC - chiral surfactant and chiral oil. Part 2: diethyl tartrate. | 2007-08 |
|
| Determination of Bitter Orange alkaloids in dietary supplements standard reference materials by liquid chromatography with ultraviolet absorbance and fluorescence detection. | 2007-07-13 |
|
| Simultaneous analysis of adrenergic amines and flavonoids in citrus peel jams and fruit juices by liquid chromatography: part 2. | 2007-06-22 |
|
| Determination of synephrine in weight-loss products using high performance liquid chromatography with acidic potassium permanganate chemiluminescence detection. | 2007-06-12 |
|
| A case of severe exercise-induced rhabdomyolysis associated with a weight-loss dietary supplement. | 2007-06 |
|
| Two-chiral-component microemulsion electrokinetic chromatography-chiral surfactant and chiral oil: part 1. dibutyl tartrate. | 2007-06 |
|
| Biochemistry of neuromodulation in primary headaches: focus on anomalies of tyrosine metabolism. | 2007-05 |
|
| Determination of synephrine in bitter orange raw materials, extracts, and dietary supplements by liquid chromatography with ultraviolet detection: single-laboratory validation. | 2007-03-22 |
|
| Detection and validated quantification of nine herbal phenalkylamines and methcathinone in human blood plasma by LC-MS/MS with electrospray ionization. | 2007-02 |
|
| Anti-inflammatory effects and mechanisms of the ethanol extract of Evodia rutaecarpa and its bioactive components on neutrophils and microglial cells. | 2007-01-26 |
|
| Evaluation of the stimulant content of dietary supplements marketed as "ephedra-free". | 2007 |
|
| Reporting associations between dietary supplements and adverse events. | 2006-12 |
|
| Chemical and biological comparisons on Evodia with two related species of different locations and conditions. | 2006-11-24 |
|
| Chemiluminescence of synephrine based on the cerium(IV)-rhodamine B system. | 2006-11-08 |
|
| A new method for fabrication of an integrated indium tin oxide electrode on electrophoresis microchips with amperometric detection and its application for determination of synephrine and hesperidin in pericarpium citri reticulatae. | 2006-11 |
|
| Consumption of dietary supplements containing Citrus aurantium (bitter orange)--2004 California Behavioral Risk Factor Surveillance Survey (BRFSS). | 2006-10 |
|
| Determination of octopamine, synephrine and tyramine in Citrus herbs by ionic liquid improved 'green' chromatography. | 2006-09-01 |
|
| [Determination of three chemical components in Fructus aurantii immaturus]. | 2006-09 |
|
| Strategies for enantioseparations of catecholamines and structurally related compounds by capillary zone electrophoresis using sulfated beta-cyclodextrins as chiral selectors. | 2006-09 |
|
| Abnormal platelet trace amine profiles in migraine with and without aura. | 2006-08 |
|
| A rapid and simple procedure for the determination of synephrine in dietary supplements by gas chromatography-mass spectrometry. | 2006-06-16 |
|
| Thermogenic effect from nutritionally enriched coffee consumption. | 2006-06-05 |
|
| Metal content of ephedra-containing dietary supplements and select botanicals. | 2006-04-01 |
|
| Response of CEDIA amphetamines assay after a single dose of bitter orange. | 2006-04 |
|
| Variant angina associated with bitter orange in a dietary supplement. | 2006-04 |
|
| Development and validation of HPLC methods for the analysis of phenethylamine and indoloquinazoline alkaloids in Evodia species. | 2006-03 |
|
| Analysis of ephedra-free labeled dietary supplements sold in the San Francisco Bay area in 2003. | 2006 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT01423019
Two capsules are taken twice daily, 20-30 minutes before breakfast and evening meals. Two capsules contain a total of 50 mg p-synephrine.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20217639
HEK293 cells stably expressing the α1A-AR were transfected with the TRE‑LUC plasmid (40 μg/mL) using electroporation (70msec, single pulse, 150 volts). The transfected cells were seeded at a density of 50000 cells/well in microtiter plates (Cultureplate®; Packard) in 200 μL media and allowed to grow for 24 h with incubation at 37°C (5% CO2). After 24 h, the cells were treated with various drug concentrations for 20 h, which was found to be optimum during time-course analyses performed earlier. When antagonist studies were performed, the compounds (Oxedrine 1nM-1mM) were added 15min prior to the addition of the agonist L-phenylephrine. Following drug exposures, the cells were lysed, and luciferase activity was measured using the Luclite assay kit
| Substance Class |
Chemical
Created
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| Record UNII |
PEG5DP7434
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| Record Status |
Validated (UNII)
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S01GA06
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S01GA56
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2287 (Number of products:206)
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WHO-VATC |
QC01CA08
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C01CA08
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QS01GA56
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QS01FB90
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7172
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D013578
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1642609
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CHEMBL33720
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SYNEPHRINE
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m10412
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170956
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10288
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29081
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PEG5DP7434
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3577
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PARENT -> IMPURITY |
CHROMATOGRAPHIC PURITY (HPLC/UV)
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ACTIVE MOIETY |
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