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

Details

Stereochemistry RACEMIC
Molecular Formula C9H13NO2.ClH
Molecular Weight 203.666
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of OXEDRINE HYDROCHLORIDE

SMILES

Cl.CNCC(O)C1=CC=C(O)C=C1

InChI

InChIKey=COTCEGYSNTWJQV-UHFFFAOYSA-N
InChI=1S/C9H13NO2.ClH/c1-10-6-9(12)7-2-4-8(11)5-3-7;/h2-5,9-12H,6H2,1H3;1H

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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 ( + / - )

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
Characterization of antidepressant-like effects of p-synephrine stereoisomers.
2001 Jul
Determination of adrenergic agonists from extracts and herbal products of Citrus aurantium L. var. amara by LC.
2002 Aug 1
Determination of hesperidin and synephrine in Pericarpium Citri Reticulatae by capillary electrophoresis with electrochemical detection.
2002 Jun
Octopaminergic agonists for the cockroach neuronal octopamine receptor.
2003
HPLC electrochemical detection of trace amines in human plasma and platelets and expression of mRNA transcripts of trace amine receptors in circulating leukocytes.
2003 Jul 31
Screening for endogenous substrates reveals that CYP2D6 is a 5-methoxyindolethylamine O-demethylase.
2003 Jun
Moderate weight-lowering effect of octopamine treatment in obese Zucker rats.
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
Synephrine is not Neo-Synephrine.
2004 Dec
Possible association of acute lateral-wall myocardial infarction and bitter orange supplement.
2004 May
Elevated levels of circulating trace amines in primary headaches.
2004 May 25
Quantitative and qualitative HPLC analysis of thermogenic weight loss products.
2004 Nov
Contributions of biochemistry to the pathogenesis of primary headaches.
2004 Oct
Citrus aurantium, an ingredient of dietary supplements marketed for weight loss: current status of clinical and basic research.
2004 Sep
Ischemic stroke associated with use of an ephedra-free dietary supplement containing synephrine.
2005 Apr
Enantioselective LC analysis of synephrine in natural products on a protein-based chiral stationary phase.
2005 Apr 29
A rapid liquid chromatography electrospray ionization mass spectrometry(n) method for evaluation of synephrine in Citrus aurantium L. samples.
2005 Dec 28
Molecular mechanisms of toxicity of important food-borne phytotoxins.
2005 Feb
Hemodynamic effects of ephedra-free weight-loss supplements in humans.
2005 Sep
Reporting associations between dietary supplements and adverse events.
2006 Dec
Quantitative and qualitative analysis of flavonoid markers in Frucus aurantii of different geographical origin by capillary electrophoresis with electrochemical detection.
2006 Jan 18
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
Metabolic and physiological effects of ingesting extracts of bitter orange, green tea and guarana at rest and during treadmill walking in overweight males.
2006 May
[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
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
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
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
Determination of bitter orange alkaloids in dietary supplement Standard Reference Materials by liquid chromatography with atmospheric-pressure ionization mass spectrometry.
2007 Sep
In vitro anticholinesterase activity of various alkaloids.
2007 Sep-Oct
Citrus aurantium--beware of the bitter orange.
2008 Jul
Sensitive determination of norepinephrine, synephrine, and isoproterenol by capillary electrophoresis with indirect electrochemiluminescence detection.
2008 Jul
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
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 Dec 15 15:19:08 UTC 2023
Edited
by admin
on Fri Dec 15 15:19:08 UTC 2023
Record UNII
EN5D1IH09S
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
OXEDRINE HYDROCHLORIDE
MART.   WHO-DD  
Common Name English
SYNEPHRINE HYDROCHLORIDE [MI]
Common Name English
SYNEPHRINE HYDROCHLORIDE
MI  
Common Name English
Oxedrine hydrochloride [WHO-DD]
Common Name English
OXEDRINE HYDROCHLORIDE [MART.]
Common Name English
OXEDRINE HCL
Common Name English
(RS)-1-(4-HYDROXYPHENYL)-2-(METHYLAMINO)ETHANOL HYDROCHLORIDE
Systematic Name English
Code System Code Type Description
SMS_ID
100000087306
Created by admin on Fri Dec 15 15:19:08 UTC 2023 , Edited by admin on Fri Dec 15 15:19:08 UTC 2023
PRIMARY
PUBCHEM
22302
Created by admin on Fri Dec 15 15:19:08 UTC 2023 , Edited by admin on Fri Dec 15 15:19:08 UTC 2023
PRIMARY
EPA CompTox
DTXSID70975251
Created by admin on Fri Dec 15 15:19:08 UTC 2023 , Edited by admin on Fri Dec 15 15:19:08 UTC 2023
PRIMARY
MERCK INDEX
m10412
Created by admin on Fri Dec 15 15:19:08 UTC 2023 , Edited by admin on Fri Dec 15 15:19:08 UTC 2023
PRIMARY Merck Index
CAS
5985-28-4
Created by admin on Fri Dec 15 15:19:08 UTC 2023 , Edited by admin on Fri Dec 15 15:19:08 UTC 2023
PRIMARY
WIKIPEDIA
Synephrine hydrochloride
Created by admin on Fri Dec 15 15:19:08 UTC 2023 , Edited by admin on Fri Dec 15 15:19:08 UTC 2023
PRIMARY
ECHA (EC/EINECS)
227-804-6
Created by admin on Fri Dec 15 15:19:08 UTC 2023 , Edited by admin on Fri Dec 15 15:19:08 UTC 2023
PRIMARY
FDA UNII
EN5D1IH09S
Created by admin on Fri Dec 15 15:19:08 UTC 2023 , Edited by admin on Fri Dec 15 15:19:08 UTC 2023
PRIMARY
EVMPD
SUB20984
Created by admin on Fri Dec 15 15:19:08 UTC 2023 , Edited by admin on Fri Dec 15 15:19:08 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE