Details
Stereochemistry | EPIMERIC |
Molecular Formula | 2C9H13NO2.C4H6O6 |
Molecular Weight | 484.4969 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 2 / 4 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
O[C@H]([C@@H](O)C(O)=O)C(O)=O.CNCC(O)C1=CC=C(O)C=C1.CNCC(O)C2=CC=C(O)C=C2
InChI
InChIKey=KZZBAIXGUQOHKI-CEAXSRTFSA-N
InChI=1S/2C9H13NO2.C4H6O6/c2*1-10-6-9(12)7-2-4-8(11)5-3-7;5-1(3(7)8)2(6)4(9)10/h2*2-5,9-12H,6H2,1H3;1-2,5-6H,(H,7,8)(H,9,10)/t;;1-,2-/m..1/s1
Molecular Formula | C4H6O6 |
Molecular Weight | 150.0868 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
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 Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: Page: p.5 |
healthy, 22.3 ± 1.6 n = 12 Health Status: healthy Age Group: 22.3 ± 1.6 Sex: M Population Size: 12 Sources: Page: p.5 |
|
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 Co-administed with:: caffeine, p.o(400 mg, q.d, 2 weeks) Sources: Page: p.11 |
healthy, 27 n = 1 Health Status: healthy Age Group: 27 Sex: F Population Size: 1 Sources: Page: p.11 |
Disc. AE: Ventricular fibrillation... AEs leading to discontinuation/dose reduction: Ventricular fibrillation Sources: Page: p.11 |
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 Co-administed with:: caffeine, p.o(400 mg, q.d, 2 weeks) Sources: Page: p.11 |
healthy, 27 n = 1 Health Status: healthy Age Group: 27 Sex: F Population Size: 1 Sources: Page: p.11 |
PubMed
Title | Date | PubMed |
---|---|---|
Characterization of antidepressant-like effects of p-synephrine stereoisomers. | 2001 Jul |
|
Screening for endogenous substrates reveals that CYP2D6 is a 5-methoxyindolethylamine O-demethylase. | 2003 Jun |
|
Elusive amines and primary headaches: historical background and prospectives. | 2003 May |
|
Electrical storm: case series and review of management. | 2003 Sep |
|
Determination of ephedrine alkaloids and synephrine in dietary supplements by column-switching cation exchange high-performance liquid chromatography with scanning-wavelength ultraviolet and fluorescence detection. | 2003 Sep 10 |
|
Ephedra-free is not danger-free. | 2003 Sep 19 |
|
Bitter orange weight loss products may not be safe. | 2004 Dec |
|
Quantitative and qualitative HPLC analysis of thermogenic weight loss products. | 2004 Nov |
|
Safety and efficacy of citrus aurantium for weight loss. | 2004 Nov 15 |
|
Elusive amines and cluster headache: mutational analysis of trace amine receptor cluster on chromosome 6q23. | 2004 Oct |
|
Products containing bitter orange or synephrine: suspected cardiovascular adverse reactions. | 2004 Oct 12 |
|
Citrus aurantium, an ingredient of dietary supplements marketed for weight loss: current status of clinical and basic research. | 2004 Sep |
|
Exactly which synephrine alkaloids does Citrus aurantium (bitter orange) contain? | 2005 Apr |
|
Enantioselective LC analysis of synephrine in natural products on a protein-based chiral stationary phase. | 2005 Apr 29 |
|
Comment on Citrus aurantium Minireview. | 2005 Feb |
|
The presence of trace amines in postmortem cerebrospinal fluid in humans. | 2005 May |
|
Determination of ephedrine alkaloids in dietary supplement standard reference materials. | 2005 May 15 |
|
Rational method development strategies on a fluorinated liquid chromatography stationary phase: mobile phase ion concentration and temperature effects on the separation of ephedrine alkaloids. | 2005 Nov 18 |
|
Hemodynamic effects of ephedra-free weight-loss supplements in humans. | 2005 Sep |
|
Analysis of ephedra-free labeled dietary supplements sold in the San Francisco Bay area in 2003. | 2006 |
|
Response of CEDIA amphetamines assay after a single dose of bitter orange. | 2006 Apr |
|
Metal content of ephedra-containing dietary supplements and select botanicals. | 2006 Apr 1 |
|
Citrus aurantium and synephrine alkaloids in the treatment of overweight and obesity: an update. | 2006 Feb |
|
Blood pressure and heart rate effects following a single dose of bitter orange. | 2006 Jan |
|
Sensitive determination of synephrine by flow-injection chemiluminescence. | 2006 Jan-Feb |
|
Acute tubular necrosis associated with chromium picolinate-containing dietary supplement. | 2006 Mar |
|
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 Nov |
|
Strategies for enantioseparations of catecholamines and structurally related compounds by capillary zone electrophoresis using sulfated beta-cyclodextrins as chiral selectors. | 2006 Sep |
|
Determination of octopamine, synephrine and tyramine in Citrus herbs by ionic liquid improved 'green' chromatography. | 2006 Sep 1 |
|
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 Aug |
|
Two-chiral component microemulsion EKC - chiral surfactant and chiral oil. Part 2: diethyl tartrate. | 2007 Aug |
|
Trace amine-associated receptor 1-Family archetype or iconoclast? | 2007 Dec |
|
Effects of ingesting JavaFit Energy Extreme functional coffee on aerobic and anaerobic fitness markers in recreationally-active coffee consumers. | 2007 Dec 8 |
|
Detection and validated quantification of nine herbal phenalkylamines and methcathinone in human blood plasma by LC-MS/MS with electrospray ionization. | 2007 Feb |
|
A case of severe exercise-induced rhabdomyolysis associated with a weight-loss dietary supplement. | 2007 Jun |
|
Determination of synephrine in weight-loss products using high performance liquid chromatography with acidic potassium permanganate chemiluminescence detection. | 2007 Jun 12 |
|
Chemiluminescence of synephrine based on the cerium(IV)-rhodamine B system. | 2007 Mar-Apr |
|
Mass spectrometric determination of the predominant adrenergic protoalkaloids in bitter orange (Citrus aurantium). | 2007 Nov 28 |
|
Temperature effects on the enantioselectivity of basic analytes in capillary EKC using sulfated beta-CDs as chiral selectors. | 2007 Oct |
|
Simultaneous determination of flavonoid and alkaloid compounds in Citrus herbs by high-performance liquid chromatography-photodiode array detection-electrospray mass spectrometry. | 2007 Oct 1 |
|
Fast high-performance liquid chromatography analysis of phenethylamine alkaloids in Citrus natural products on a pentafluorophenylpropyl stationary phase. | 2007 Sep 21 |
|
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 Aug |
|
Effects of chemopreventive citrus phytochemicals on human P-glycoprotein and multidrug resistance protein 1. | 2008 Dec 14 |
|
Vasospasm and stroke attributable to ephedra-free xenadrine: case report. | 2008 Jul |
|
Certification of standard reference materials containing bitter orange. | 2008 Jul |
|
Human pharmacology of a performance-enhancing dietary supplement under resting and exercise conditions. | 2008 Jun |
|
Synephrine content of juice from Satsuma mandarins (Citrus unshiu Marcovitch). | 2008 Oct 8 |
|
Determination of ephedrine alkaloids in Ephedra natural products using HPLC on a pentafluorophenylpropyl stationary phase. | 2008 Sep 29 |
|
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 Jan |
|
Selectivity and potential interference from phenolic compounds in chemiluminescence methods for the determination of synephrine. | 2009 Mar-Apr |
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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admin
on
Edited
Fri Dec 15 18:30:16 GMT 2023
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on
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Record UNII |
9I99I5995J
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Record Status |
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Record Version |
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