U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C9H13NO2
Molecular Weight 167.2054
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of OXEDRINE

SMILES

CNCC(c1ccc(cc1)O)O

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

HIDE SMILES / InChI

Molecular Formula C9H13NO2
Molecular Weight 167.2054
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description
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

Sources: Archiv fuer Experimentelle Pathologie und Pharmakologie (1927), 124, 231-44.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
6.6 µM [EC50]
4.11 null [pKi]
4.44 null [pKi]
4.61 null [pKi]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Advantra Z

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.75 ng/mL
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
427.9 ng × min/mL
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
2.56 h
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
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

Doses

DosePopulationAdverse 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
Disc. AE: Ventricular fibrillation...
AEs leading to
discontinuation/dose reduction:
Ventricular fibrillation
Sources: Page: p.11
AEs

AEs

AESignificanceDosePopulation
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
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
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
Variant angina associated with bitter orange in a dietary supplement.
2006 Apr
Metal content of ephedra-containing dietary supplements and select botanicals.
2006 Apr 1
Abnormal platelet trace amine profiles in migraine with and without aura.
2006 Aug
Reporting associations between dietary supplements and adverse events.
2006 Dec
A rapid and simple procedure for the determination of synephrine in dietary supplements by gas chromatography-mass spectrometry.
2006 Jun 16
Thermogenic effect from nutritionally enriched coffee consumption.
2006 Jun 5
Development and validation of HPLC methods for the analysis of phenethylamine and indoloquinazoline alkaloids in Evodia species.
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
Chemical and biological comparisons on Evodia with two related species of different locations and conditions.
2006 Nov 24
Consumption of dietary supplements containing Citrus aurantium (bitter orange)--2004 California Behavioral Risk Factor Surveillance Survey (BRFSS).
2006 Oct
[Determination of three chemical components in Fructus aurantii immaturus].
2006 Sep
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
Evaluation of the stimulant content of dietary supplements marketed as "ephedra-free".
2007
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
Chromatographic and electrophoretic methods for the analysis of phenethylamine [corrected] alkaloids in Citrus aurantium.
2007 Aug 17
Lipolysis induced by segment wall extract from Satsuma mandarin orange (Citrus unshu Mark).
2007 Dec
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
Anti-inflammatory effects and mechanisms of the ethanol extract of Evodia rutaecarpa and its bioactive components on neutrophils and microglial cells.
2007 Jan 26
Determination of synephrine in bitter orange raw materials, extracts, and dietary supplements by liquid chromatography with ultraviolet detection: single-laboratory validation.
2007 Jan-Feb
Determination of Bitter Orange alkaloids in dietary supplements standard reference materials by liquid chromatography with ultraviolet absorbance and fluorescence detection.
2007 Jul 13
A case of severe exercise-induced rhabdomyolysis associated with a weight-loss dietary supplement.
2007 Jun
Two-chiral-component microemulsion electrokinetic chromatography-chiral surfactant and chiral oil: part 1. dibutyl tartrate.
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
Biochemistry of neuromodulation in primary headaches: focus on anomalies of tyrosine metabolism.
2007 May
Simultaneous analysis of adrenergic amines and flavonoids in citrus peel jams and fruit juices by liquid chromatography: part 2.
2007 May-Jun
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
Determination of bitter orange alkaloids in dietary supplement Standard Reference Materials by liquid chromatography with atmospheric-pressure ionization mass spectrometry.
2007 Sep
Fast high-performance liquid chromatography analysis of phenethylamine alkaloids in Citrus natural products on a pentafluorophenylpropyl stationary phase.
2007 Sep 21
In vitro anticholinesterase activity of various alkaloids.
2007 Sep-Oct
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
Citrus aurantium--beware of the bitter orange.
2008 Jul
Vasospasm and stroke attributable to ephedra-free xenadrine: case report.
2008 Jul
Sensitive determination of norepinephrine, synephrine, and isoproterenol by capillary electrophoresis with indirect electrochemiluminescence detection.
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
Coronary spasm and thrombosis in a bodybuilder using a nutritional supplement containing synephrine, octopamine, tyramine and caffeine.
2008 May
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

Patents

Sample Use Guides

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
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
by admin
on Fri Jun 25 23:17:00 UTC 2021
Edited
by admin
on Fri Jun 25 23:17:00 UTC 2021
Record UNII
PEG5DP7434
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
OXEDRINE
MART.   WHO-DD  
Common Name English
PARASYMPATOL
Brand Name English
(+/-)-OXEDRINE
Common Name English
P-SYNEPHRINE
Common Name English
DL-SYNEPHRINE
Common Name English
ANALEPTIN
Common Name English
(+/-)-SYNEPHRINE
Common Name English
SYNTHENATE
Brand Name English
(RS)-1-(4-HYDROXYPHENYL)-2-(METHYLAMINO)ETHANOL
Systematic Name English
ETHAPHENE
Common Name English
BENZENEMETHANOL, 4-HYDROXY-.ALPHA.-((METHYLAMINO)METHYL)-
Systematic Name English
SIMPALON
Brand Name English
NSC-170956
Code English
ADVANTRA Z
Brand Name English
OXEDRINE [USP]
Common Name English
NSC-166285
Code English
SYNEPHRINE [MI]
Common Name English
SYNEPHRIN
Common Name English
SYNEPHRINE
INCI   MI  
INCI  
Official Name English
S-38537-9
Code English
SYNEPHRINE [USP-RS]
Common Name English
SYNEPHRINE [INCI]
Common Name English
OXEDRINE [WHO-DD]
Common Name English
OXEDRINE [MART.]
Common Name English
Classification Tree Code System Code
WHO-ATC S01GA06
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
WHO-VATC QS01GA06
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
WHO-ATC S01GA56
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
DSLD 2287 (Number of products:206)
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
WHO-VATC QC01CA08
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
WHO-ATC C01CA08
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
WHO-VATC QS01GA56
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
WHO-VATC QS01FB90
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
Code System Code Type Description
PUBCHEM
7172
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
PRIMARY
MESH
D013578
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
PRIMARY
ChEMBL
CHEMBL33720
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
PRIMARY
WIKIPEDIA
SYNEPHRINE
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
PRIMARY
MERCK INDEX
M10412
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
PRIMARY Merck Index
USP_CATALOG
1642609
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
PRIMARY USP-RS
RXCUI
10288
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
PRIMARY RxNorm
ECHA (EC/EINECS)
202-300-9
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
PRIMARY
EPA CompTox
94-07-5
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
PRIMARY
EVMPD
SUB14726MIG
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
PRIMARY
CAS
94-07-5
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
PRIMARY
DRUG BANK
DB09203
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
PRIMARY
FDA UNII
PEG5DP7434
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
PRIMARY
DRUG CENTRAL
3577
Created by admin on Fri Jun 25 23:17:01 UTC 2021 , Edited by admin on Fri Jun 25 23:17:01 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> AGONIST
SALT/SOLVATE -> PARENT
Related Record Type Details
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
ACTIVE MOIETY