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Oxymetazoline

PubChem CID
4636
Structure
Oxymetazoline_small.png
Oxymetazoline_3D_Structure.png
Molecular Formula
Synonyms
  • oxymetazoline
  • 1491-59-4
  • Oxymethazoline
  • Hazol
  • Oximetazolinum
Molecular Weight
260.37 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-03-25
  • Modify:
    2025-01-04
Description
Oxymetazoline is a member of the class of phenols that is 2,4-dimethylphenol which is substituted at positions 3 and 6 by 4,5-dihydro-1H-imidazol-2-ylmethyl and tert-butyl groups, respectively. A direct-acting sympathomimetic with marked alpha-adrenergic activity, it is a vasoconstrictor that is used (generally as the hydrochloride salt) to relieve nasal congestion. It has a role as an alpha-adrenergic agonist, a sympathomimetic agent, a nasal decongestant and a vasoconstrictor agent. It is a member of phenols, a carboxamidine and a member of imidazolines. It is a conjugate base of an oxymetazoline(1+).
Oxymetazoline is an imidazole derivative and a potent, direct-acting alpha (α)-adrenergic agonist with affinity to both α1- and α2-adrenoceptors. Oxymetazoline is available in various formulations with a wide variety of clinical implications. The topical formulation of the drug is used to treat persistent facial redness in adults. As an effective decongestant, oxymetazoline is available in over-the-counter intranasal sprays used to relieve nasal and sinus congestion caused by a wide variety of conditions, such as common cold, hay fever, and upper respiratory allergies. In dentistry, oxymetazoline and tetracaine combination intranasal spray (Kovanaze) is used for regional anesthesia during dental procedures in children and adults. In July 2020, the FDA approved the use of an ophthalmic formulation of oxymetazoline (Upneeq) in adults with acquired blepharoptosis, or ptosis, making it the first FDA-approved medical treatment for this medical condition.
Oxymetazoline is a Vasoconstrictor. The physiologic effect of oxymetazoline is by means of Vasoconstriction, and Increased Sympathetic Activity.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Oxymetazoline.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

6-tert-butyl-3-(4,5-dihydro-1H-imidazol-2-ylmethyl)-2,4-dimethylphenol
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C16H24N2O/c1-10-8-13(16(3,4)5)15(19)11(2)12(10)9-14-17-6-7-18-14/h8,19H,6-7,9H2,1-5H3,(H,17,18)
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

WYWIFABBXFUGLM-UHFFFAOYSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

CC1=CC(=C(C(=C1CC2=NCCN2)C)O)C(C)(C)C
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C16H24N2O
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

1491-59-4

2.3.2 European Community (EC) Number

2.3.3 UNII

2.3.4 ChEBI ID

2.3.5 ChEMBL ID

2.3.6 DrugBank ID

2.3.7 DSSTox Substance ID

2.3.8 HMDB ID

2.3.9 KEGG ID

2.3.10 Metabolomics Workbench ID

2.3.11 NCI Thesaurus Code

2.3.12 Nikkaji Number

2.3.13 PharmGKB ID

2.3.14 Pharos Ligand ID

2.3.15 RXCUI

2.3.16 Wikidata

2.3.17 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • Hydrochloride, Oxymetazoline
  • Oxymetazoline
  • Oxymetazoline Hydrochloride

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
260.37 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3-AA
Property Value
2.9
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
260.188863393 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
260.188863393 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
44.6 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
19
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
345
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Physical Description

Solid

3.2.2 Color / Form

Crystals from benzene
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 10th ed. Volumes 1-3 New York, NY: John Wiley & Sons Inc., 1999., p. 2805

3.2.3 Melting Point

182 °C
PhysProp
181-183 °C
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1247
182 °C

3.2.4 Solubility

ODORLESS; WHITE TO NEARLY WHITE, FINE, CRYSTALLINE POWDER; SOL IN ALC
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 818
Mol wt 296.84. Crystals, dec 300-303 °C. Freely sol in water, alcohol. Practically insol in ether, chloroform, benzene /Hydrochloride/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1247
Insoluble in diethyl ether, chloroform, and benzene
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 10th ed. Volumes 1-3 New York, NY: John Wiley & Sons Inc., 1999., p. 2805
5.15e-02 g/L

3.2.5 LogP

3.4
3.4

3.2.6 Stability / Shelf Life

STABLE IN LIGHT & HEAT, & IS NONHYGROSCOPIC /HYDROCHLORIDE/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 818

3.2.7 Decomposition

When heated to decomposition it emits toxic fumes of /nitrogen oxides/.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2807

3.2.8 Collision Cross Section

168.16 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

160.2 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

162.92 Ų [M+H-H2O]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

163.86 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Ross et al. JASMS 2022; 33; 1061-1072. DOI:10.1021/jasms.2c00111

3.2.9 Kovats Retention Index

Standard non-polar
2123 , 2170 , 2168

3.3 Chemical Classes

3.3.1 Drugs

Pharmaceuticals
S10 | SWISSPHARMA | Pharmaceutical List with Consumption Data | DOI:10.5281/zenodo.2623484
Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
3.3.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Adrenergic alpha-Agonists; Sympathomimetics; Nasal Decongestants
Human drug -> None (Tentative Approval); Active ingredient (OXYMETAZOLINE)
Pharmaceuticals
S72 | NTUPHTW | Pharmaceutically Active Substances from National Taiwan University | DOI:10.5281/zenodo.3955664

4 Spectral Information

4.1 Mass Spectrometry

4.1.1 GC-MS

1 of 8
View All
NIST Number
113855
Library
Main library
Total Peaks
130
m/z Top Peak
245
m/z 2nd Highest
260
m/z 3rd Highest
217
Thumbnail
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2 of 8
View All
NIST Number
246489
Library
Replicate library
Total Peaks
127
m/z Top Peak
245
m/z 2nd Highest
260
m/z 3rd Highest
217
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4.1.2 MS-MS

NIST Number
1182721
Instrument Type
IT/ion trap
Collision Energy
0
Spectrum Type
MS2
Precursor Type
[M+H]+
Precursor m/z
261.1961
Total Peaks
26
m/z Top Peak
205.1
m/z 2nd Highest
261.1
m/z 3rd Highest
177.1
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4.1.3 LC-MS

1 of 16
View All
Authors
Kevin S. Jewell; Björn Ehlig; Arne Wick
Instrument
TripleTOF 5600 SCIEX
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
30
Fragmentation Mode
CID
Column Name
Zorbax Eclipse Plus C18 2.1 mm x 150 mm, 3.5 um, Agilent
Retention Time
7.429 min
Precursor m/z
261.1961
Precursor Adduct
[M+H]+
Top 5 Peaks

261.1965 999

205.1343 399

177.1277 34

191.1429 27

135.0808 25

Thumbnail
Thumbnail
License
dl-de/by-2-0
2 of 16
View All
Authors
Kevin S. Jewell; Björn Ehlig; Arne Wick
Instrument
TripleTOF 5600 SCIEX
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
50
Fragmentation Mode
CID
Column Name
Zorbax Eclipse Plus C18 2.1 mm x 150 mm, 3.5 um, Agilent
Retention Time
7.429 min
Precursor m/z
261.1961
Precursor Adduct
[M+H]+
Top 5 Peaks

135.0815 999

231.1491 826

161.0967 748

205.1336 645

105.071 493

Thumbnail
Thumbnail
License
dl-de/by-2-0

4.2 IR Spectra

4.2.1 ATR-IR Spectra

Instrument Name
Bio-Rad FTS
Technique
ATR-Film (MeCl2) (DuraSamplIR II)
Source of Spectrum
Forensic Spectral Research
Source of Sample
Spectrum Chemical Manufacturing Corp.
Catalog Number
Free base of O1359
Lot Number
Free base of XS3207
Copyright
Copyright © 2012-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.3 Other Spectra

Intense mass spectral peaks: 81 m/z, 217 m/z, 245 m/z, 260 m/z
Pfleger, K., H. Maurer and A. Weber. Mass Spectral and GC Data of Drugs, Poisons and their Metabolites. Parts I and II. Mass Spectra Indexes. Weinheim, Federal Republic of Germany. 1985., p. 436

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

Oxymetazoline is indicated for the topical treatment of persistent facial erythema associated with rosacea in adults. Ophthalmic oxymetazoline is indicated for the treatment of acquired blepharoptosis in adults. When used in combination with tetracaine intranasally, oxymetazoline is indicated for regional anesthesia when performing a restorative procedure on Teeth 4-13 and A-J in adults and children who weigh 40 kg or more. Oxymetazoline can be found in over-the-counter nasal products as a nasal decongestant. For off-label uses, oxymetazoline has been used during nasal intubation and during ear, nose, and throat surgery to improve visualization of the airway and to minimize post-operative bleeding.

7.2 Drug Classes

Breast Feeding; Lactation; Milk, Human; Adrenergic alpha-Agonists; Sympathomimetics; Nasal Decongestants

7.3 FDA Approved Drugs

7.4 FDA National Drug Code Directory

7.5 Drug Labels

Drug and label
Active ingredient and drug

7.6 Clinical Trials

7.6.1 ClinicalTrials.gov

7.6.2 EU Clinical Trials Register

7.7 Therapeutic Uses

Adrenergic alpha-Agonists; Nasal Decongestants; Sympathomimetics
National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)
Adrenergic (vasoconstrictor); nasal decongestant
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1247
Oxymetazoline /ophthalmic/ is indicated for temporary relief of redness associated with minor irritations of the eye, such as those caused by pollen-related allergies colds, dust, smog, wind, swimming, or wearing contact lenses. /Included in US product labeling/
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2320
Nasal oxymetazoline is used for the relief of sinus congestion. /NOT included in US product labeling/
USP Convention. USPDI - Drug Information for the Health Care Professional. 16th ed. Volume I. Rockville, MD: U.S. Pharmaceutical Convention, Inc. 1996 (Plus updates)., p. 2261
For more Therapeutic Uses (Complete) data for OXYMETAZOLINE (11 total), please visit the HSDB record page.

7.8 Drug Warnings

Intranasal use of oxymetazoline may occasionally cause systemic sympathomimetic effects such as hypertension, nervousness, nausea, dizziness, headache, insomnia, palpitation, or reflex bradycardia.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 2824
Intranasal administration of oxymetazoline may cause transient burning, stinging, increased nasal discharge or dryness of the nasal mucosa, and sneezing. Rebound congestion, characterized by chronic redness, swelling, and rhinitis, frequently occurs with prolonged use and may result in overuse of the drug. Prolonged use of nasal decongestant solutions should be avoided for these reasons.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 2824
The incidence of serious adverse effects is low in patients receiving therapeutic dosages of topical oxymetazoline hydrochloride.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 2824
Safe use of oxymetazoline during pregnancy has not been established. Oxymetazoline hydrochloride ophthalmic or nasal solutions should be used during pregnancy only when instructed by a clinician.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 2824
For more Drug Warnings (Complete) data for OXYMETAZOLINE (13 total), please visit the HSDB record page.

8 Pharmacology and Biochemistry

8.1 Pharmacodynamics

Oxymetazoline is an adrenergic α1- and α2-agonist and a direct-acting sympathomimetic drug. By stimulating adrenergic receptors, oxymetazoline causes vasoconstriction of dilated arterioles and reduces blood flow. In a radioligand competition study, oxymetazoline displayed higher affinity at α1A-adrenoceptors compared to α2B-adrenoceptors, but with higher potency at α2B-adrenoceptors. When sprayed intranasally, oxymetazoline relieved relief nasal congestion and improved nasal airflow in patients with acute coryzal rhinitis for up to 12 hours following a single dose. An early _in vitro_ study demonstrated oxymetazoline to exert anti-oxidant actions, where it inhibited microsomal lipid peroxidation and mediated hydroxyl radical scavenging activity. This suggests that oxymetazoline has a beneficial effect against oxidants, which play a role in tissue damage in inflammation.

8.2 MeSH Pharmacological Classification

Adrenergic alpha-Agonists
Drugs that selectively bind to and activate alpha adrenergic receptors. (See all compounds classified as Adrenergic alpha-Agonists.)
Nasal Decongestants
Drugs designed to treat inflammation of the nasal passages, generally the result of an infection (more often than not the common cold) or an allergy related condition, e.g., hay fever. The inflammation involves swelling of the mucous membrane that lines the nasal passages and results in inordinate mucus production. The primary class of nasal decongestants are vasoconstrictor agents. (From PharmAssist, The Family Guide to Health and Medicine, 1993) (See all compounds classified as Nasal Decongestants.)
Sympathomimetics
Drugs that mimic the effects of stimulating postganglionic adrenergic sympathetic nerves. Included here are drugs that directly stimulate adrenergic receptors and drugs that act indirectly by provoking the release of adrenergic transmitters. (See all compounds classified as Sympathomimetics.)

8.3 FDA Pharmacological Classification

1 of 2
FDA UNII
8VLN5B44ZY
Active Moiety
OXYMETAZOLINE
Pharmacological Classes
Established Pharmacologic Class [EPC] - Vasoconstrictor
Pharmacological Classes
Physiologic Effects [PE] - Vasoconstriction
Pharmacological Classes
Physiologic Effects [PE] - Increased Sympathetic Activity
Pharmacological Classes
Chemical Structure [CS] - Imidazolines
FDA Pharmacology Summary
Oxymetazoline is a Vasoconstrictor. The physiologic effect of oxymetazoline is by means of Vasoconstriction, and Increased Sympathetic Activity.
2 of 2
Non-Proprietary Name
OXYMETAZOLINE
Pharmacological Classes
Increased Sympathetic Activity [PE]; Imidazolines [CS]; Vasoconstrictor [EPC]; Vasoconstriction [PE]

8.4 ATC Code

S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355

S - Sensory organs

S01 - Ophthalmologicals

S01G - Decongestants and antiallergics

S01GA - Sympathomimetics used as decongestants

S01GA04 - Oxymetazoline

R - Respiratory system

R01 - Nasal preparations

R01A - Decongestants and other nasal preparations for topical use

R01AA - Sympathomimetics, plain

R01AA05 - Oxymetazoline

R - Respiratory system

R01 - Nasal preparations

R01A - Decongestants and other nasal preparations for topical use

R01AB - Sympathomimetics, combinations excl. corticosteroids

R01AB07 - Oxymetazoline

D - Dermatologicals

D11 - Other dermatological preparations

D11A - Other dermatological preparations

D11AX - Other dermatologicals

D11AX27 - Oxymetazoline

8.5 Absorption, Distribution and Excretion

Absorption
Imidazole derivatives such as oxymetazoline are readily absorbed across mucosal membranes, especially in children. In adult subjects with erythema associated with rosacea, the mean ± standard deviation (SD) Cmax was 60.5 ± 53.9 pg/mL and the AUC from time 0 to 24 hours (AUC0-24hr) was 895 ±798 pg x hr/mL following topical administration of first-dose oxymetazoline. Following once-daily topical applications for 28 days, the mean ± SD Cmax was 66.4 ± 67.1 pg/mL and the AUC0-24hr was 1050 ± 992 pg x hr/mL. Following twice-daily applications for 28 days, the mean ± SD Cmax was 68.8 ± 61.1 pg/mL and the AUC0-24hr was 1530 ± 922 pg x hr/mL. Following single-drop ocular administration of oxymetazoline in healthy adult subjects, the mean ± SD Cmax was 30.5 ± 12.7 pg/mL and the area under the concentration-time curve (AUCinf) was 468 ± 214 pg x hr/mL. The median Tmax was 2 hours, ranging from 0.5 to 12 hours. Following nasal administration of an 0.6 mL combination product containing tetracaine and oxymetazoline in adult subjects, the maximum concentrations of oxymetazoline were reached within approximately 10 minutes. The mean Cmax was 1.78 ng/mL and the AUC0-inf value was 4.24 ng x h/mL, with a median Tmax of 5 minutes.
Route of Elimination
While the excretion of oxymetazoline following nasal, topical, or ophthalmic administration of oxymetazoline has not been fully characterized in humans, it is believed that the predominant route of elimination at clinically relevant concentrations of oxymetazoline is renal excretion.
Volume of Distribution
There is limited information on the volume of distribution of oxymetazoline.
Clearance
There is limited information on the clearance rate of oxymetazoline.
... Oxymetazoline /at an optimum strength of 0.025%/ was absorbed slowly into the eye: only 0.006% of the original drug concentration was found in the aqueous humors of rabbits 30 minutes after instillation; the balance remained primarily in external ocular tissues. Metabolic studies in rabbits indicated that excreted amounts of unmetabolized radioactive oxymetazoline in urine following drug administration were similar (23%) for the ocular and nasal routes of application. The proportions of oxymetazoline metabolite to unchanged oxymetazoline were constant for all administration routes tested.
Duzman F et al; Arch Ophthalmol 101 (7): 1122-6 (1983).
Following intranasal application of oxymetazoline hydrochloride solutions, local vasoconstriction usually occurs within 5-10 minutes and persists for 5-6 hours with a gradual decline over the next 6 hours. Following topical application of oxymetazoline hydrochloride ophthalmic solution, local vasoconstriction usually occurs within minutes and may persist for up to 6 hours. Occasionally, enough oxymetazoline may be absorbed to produce systemic effects.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 2825

8.6 Metabolism / Metabolites

_In vitro_, oxymetazoline was minimally metabolized by human liver enzymes to produce mono-oxygenated and dehydrogenated metabolites. About 95.9% of the total dose of oxymetazoline remained as an unchanged parent compound after a 120-minute incubation with human liver microsomes. When incubated in rat, rabbit, and human liver post-mitochondrial supernatant fraction from homogenized tissue (S9) fractions, oxymetazoline was more efficiently metabolized by rabbit liver S9 fractions (~65%) than by rat (~20%) or human (~10%) liver S9 fractions. At concentrations (50 μM) at least 130-fold greater than the usual therapeutic intranasal dose (400 nM), CYP2C19 was suggested to be involved in the oxidation of oxymetazoline following intranasal administration; however, metabolites in humans have not been fully characterized up to date and remain speculated based on _in vitro_ studies using rat and rabbit liver S9 fractions and microsomes. The O-glucuronide metabolite catalyzed by UGT1A9 has been identified _in vitro_.

8.7 Biological Half-Life

Following ocular administration in healthy adults, the mean terminal half-life was 8.3 hours, ranging from 5.6 to 13.9 hours. The terminal half-life of oxymetazoline following nasal administration of the combination product containing tetracaine and oxymetazoline in adult subjects is approximately 5.2 hours.

8.8 Mechanism of Action

Oxymetazoline binds to α1- and α2-adrenoceptors, which are Gq- and Gi-protein-coupled receptors respectively. α1-adrenoceptors agonism promotes vascular smooth muscle contraction by increasing intracellular calcium levels through activating phospholipase C, while α2-adrenoceptors agonism, specifically the α2B-adrenoceptors, can also elicit vasoconstriction through the inhibition of adenyl cyclase. Rosacea is a condition characterized by transient and persistent facial erythema. By stimulating α1A-adrenoceptors and causing vasoconstriction, oxymetazoline is believed to diminish the symptoms of erythema. In blepharoptosis, it is hypothesized that oxymetazoline works by stimulating α-adrenergic receptors on the Müller muscle that elevates the upper eyelid, causing muscle contraction. Oxymetazoline is used in combination with tetracaine for local anesthesia in dentistry. Such combination use adds beneficial effects: the vasoconstrictor counteracts the local anesthetic agent's vasodilatory action, thereby constricting dilated arterioles and reducing blood flow to the application area. Oxymetazoline relieves nasal congestion by vasoconstricting the respiratory microvasculature, in both resistance and capacitance blood vessels on the human nasal mucosa, leading to decreased nasal mucosal blood flow, edema, and airflow resistance.
The mechanism of action of oxymetazoline has not been conclusively determined. Most pharmacologists believe that the drug directly stimulates a-adrenergic receptors of the sympathetic nervous system and exerts little or no effect on beta-adrenergic receptors. Intranasal application of oxymetazoline results in constriction of dilated arterioles and reduction in nasal blood flow and congestion. In addition, obstructed eustachian ostia may be opened. Nasal ventilation and aeration are improved temporarily; however, rebound vasodilation and congestion usually occur to some degree. Following topical application of oxymetazoline hydrochloride ophthalmic solution, conjunctival congestion is temporarily relieved, but overuse of the drug may produce rebound hyperemia.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 2824

8.9 Human Metabolite Information

8.9.1 Cellular Locations

  • Extracellular
  • Membrane

8.10 Transformations

9 Use and Manufacturing

9.1 Uses

THERAP CAT: Adrenergic (vasoconstrictor); nasal decongestant
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1247
MEDICATION
Oxymetazoline nasal spray is a potent /alpha 2/-adrenergic agonist commonly used to vasoconstrict blood vessels in the nasal mucosa.
Thrush DN; J Clin Anesth 7 (6): 5112-4 (1995)

Use (kg; approx.) in Germany (2009): >10

Consumption (g per capita; approx.) in Germany (2009): 0.000122

Calculated removal (%): 86.2

9.1.1 Use Classification

Pharmaceuticals
S72 | NTUPHTW | Pharmaceutically Active Substances from National Taiwan University | DOI:10.5281/zenodo.3955664

9.2 Methods of Manufacturing

From (4-tert-butyl-2,6-dimethyl-3-hydroxyphenyl)acetonitrile & ethylenediamine: FRUHSTORFER, MUELLER-CALGAN...CHEM ABST 57, 4674A (1962).
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1247
6-t-Butyl-2,4-dimethylphenol + formaldehyde + sodium cyanide + ethylenediamine (chloromethylation/cyanidation/condensation)
Ashford, R.D. Ashford's Dictionary of Industrial Chemicals. London, England: Wavelength Publications Ltd., 1994., p. 659

9.3 Formulations / Preparations

Nasal: Solution: 0.05%* Afrin ( with benzalkonium chloride, povidone, and propylene glycol; with or without menthol and regular drops and spray), (Schering-Plough), Afrin No Drip Extra Moisturizing 12 Hour Pump Mist ( with benzalkonium chloride, benzyl alcohol, glycerin, and povidone), (Schering-Plough) Afrin No Drip Original 12 Hour Pump Mist ( with benzalkonium chloride, benzyl alcohol, and povidone), (Schering-Plough), Afrin No Drip Severe Congestion 12 Hour Pump Mist ( with benzalkonium chloride, benzyl alcohol, povidone, and propylene glycol), (Schering-Plough) Afrin No Drip Sinus 12 Hour Pump Mist ( with benzalkonium chloride, benzyl alcohol, and propylene glycol), (Schering-Plough), Dristan 12 Hour Nasal Spray ( with benzalkonium chloride and benzyl alcohol), (Wyeth), Duramist Plus 12 Hour Nasal Decongestant Spray ( with benzalkonium chloride), (Pfeiffer), 4-Way 12 Hour Long Lasting Spray ( with benzalkonium chloride and phenylmercuric acetate), (Bristol-Myers Squibb), Nasal Decongestant Maximum Strength Spray ( with benzalkonium chloride, povidone, and propylene glycol), (Taro), Neo-Synephrine 12 Hour Extra Moisturizing Spray ( with benzalkonium chloride, glycerin, and phenylmercuric acetate), (Bayer), Neo-Synephrine 12 Hour Long Acting Spray ( with benzalkonium chloride and phenylmercuric acetate), (Bayer), Nostrilla12 Hour Nasal Decongestant ( with benzalkonium chloride; with metered pump spray), (Insight), Vicks Sinex 12 Hour Nasal Decongestant Spray ( with benzalkonium chloride and with regular or metered pump mist spray), (Procter & Gamble).
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 2826
Ophthalmic: Solution: 0.025% Visine L.R. Eye Drops (with benzalkonium chloride), (Pfizer).
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 2826
Trade names: Ocuclear Eye Drops (Schering), Visine L.R. Eye Drops (Pfizer) /Oxymetazoline hydrochloride/
Ullmann's Encyclopedia of Industrial Chemistry. 6th ed.Vol 1: Federal Republic of Germany: Wiley-VCH Verlag GmbH & Co. 2003 to Present, p. V24 352 (2003)

9.4 General Manufacturing Information

PATENTS: GERMAN PATENT 1,117,588 (1961 TO E MERCK).
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1247
Available commercially as the free base or hydrochloride.
Ashford, R.D. Ashford's Dictionary of Industrial Chemicals. London, England: Wavelength Publications Ltd., 1994., p. 659

10 Identification

10.1 Analytic Laboratory Methods

SPECTROPHOTOMETRY, GENERAL SAMPLE. AMERICAN PHARMACEUTICAL ASSN FOUNDATION, J PHARM SCI 55, 956 (1966).
Sunshine, I. (ed.). CRC Handbook of Analytical Toxicology. Cleveland: The Chemical Rubber Co., 1969., p. 84
IDENTIFICATION OF OXYMETAZOLINE BY GAS CHROMATOGRAPHY.
BAKER K; IDENTIFICATION & CHEM CLASSIFICATION OF DRUGS BASED ON RELATIVE RESPONSE OF A NITROGEN SELECTIVE DETECTOR & FLAME IONIZATION DETECTOR IN GAS CHROMATOGRAPHIC ANALYSIS; ANAL CHEM 49 (7): 906-908 (1977)
HIGH PRESSURE LIQ CHROMATOGRAPHY USED IN ANALYSIS OF OXYMETAZOLINE.
MOLLICA ET AL; ANAL CHEM 45: 1859-1864 (1973)
Analyte: oxymetazoline hydrochloride; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards /oxymetazoline hydrochloride/
U.S. Pharmacopeia. The United States Pharmacopeia, USP 29/The National Formulary, NF 24; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p1611 (2006)
For more Analytic Laboratory Methods (Complete) data for OXYMETAZOLINE (14 total), please visit the HSDB record page.

11 Safety and Hazards

11.1 Hazards Identification

11.1.1 GHS Classification

Pictogram(s)
Corrosive
Acute Toxic
Signal
Danger
GHS Hazard Statements

H300+H330 (96.6%): Fatal if swallowed or if inhaled [Danger Acute toxicity, oral; acute toxicity, inhalation]

H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]

H318 (100%): Causes serious eye damage [Danger Serious eye damage/eye irritation]

H330 (100%): Fatal if inhaled [Danger Acute toxicity, inhalation]

H412 (100%): Harmful to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]

Precautionary Statement Codes

P260, P264, P264+P265, P270, P271, P273, P280, P284, P301+P316, P304+P340, P305+P354+P338, P316, P317, P320, P321, P330, P403+P233, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 29 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

11.1.2 Hazard Classes and Categories

Acute Tox. 1 (100%)

Eye Dam. 1 (100%)

Acute Tox. 1 (100%)

Aquatic Chronic 3 (100%)

11.2 Accidental Release Measures

11.2.1 Disposal Methods

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

11.3 Handling and Storage

11.3.1 Storage Conditions

Oxymetazoline hydrochloride nasal solutions should be stored in tight containers at a temperature less than 40 °C, preferably at 2-30 °C; freezing should be avoided. Oxymetazoline hydrochloride ophthalmic solutions should be stored at 15-30 °C. Oxymetazoline is probably degraded in the presence of aluminum and, therefore, should not be stored in aluminum containers.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 2826

11.4 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: Phenol, 3-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-6-(1,1-dimethylethyl)-2,4-dimethyl-
REACH Registered Substance

11.4.1 FDA Requirements

Nasal decongestant active ingredients. The active ingredient of the product consists of any of the following when used within the dosage limits and in the dosage forms established for each ingredient: ... Topical nasal decongestants: Oxymetazoline hydrochloride. /Oxymetazoline hydrochloride/
21 CFR 341.20; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of November 15, 2006: https://www.ecfr.gov
The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed over-the-counter drug products, incl oxymetazoline, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of November 15, 2006: https://www.fda.gov/cder/ob/

11.5 Other Safety Information

Chemical Assessment

IMAP assessments - Phenol, 3-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-6-(1,1-dimethylethyl)-2,4-dimethyl-: Environment tier I assessment

IMAP assessments - Phenol, 3-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-6-(1,1-dimethylethyl)-2,4-dimethyl-: Human health tier I assessment

11.5.1 Special Reports

Gilstrap LC, Little BB; Drugs & Pregnancy 269-75 (1992). Antihistamines, decongestants, and expectorants during pregnancy.
Smith MB, Feldman W; JAMA 269: 2256-63 (1993). Over the counter cold medications: critical review of clinical trials between 1950 and 1991.

12 Toxicity

12.1 Toxicological Information

12.1.1 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Although no information exists on the use of oxymetazoline specifically during breastfeeding, very little should reach the infant through breastmilk because of the local administration and limited absorption into the maternal bloodstream. It is recommended over oral systemic decongestants such as pseudoephedrine during breastfeeding. Topical use on the face for rosacea is unlikely to present a risk to the nursing infant.

◉ Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

◉ Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

◈ What is oxymetazoline?

Oxymetazoline is a medication in nasal sprays (sprayed into nostrils) and topical preparations (applied to skin). Oxymetazoline has been used to treat nasal congestion, eye inflammation, and skin redness. It works by making the blood vessels narrower (constricting blood vessels). Oxymetazoline can be found in prescription products and in many over the counter products, such as Afrin®, Dristan®, Nostrilla®, Rhofade®, and Vicks®.Sometimes when people find out they are pregnant, they think about changing how they take their medication, or stopping their medication altogether. However, it is important to talk with your healthcare providers before making any changes to how you take your medication. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy.

◈ I take oxymetazoline. Can it make it harder for me to get pregnant?

It is not known if oxymetazoline can make it harder to get pregnant.

◈ Does taking oxymetazoline increase the chance for miscarriage?

Miscarriage is common and can occur in any pregnancy for many different reasons. Studies have not been done to see if oxymetazoline increases the chance for miscarriage.

◈ Does taking oxymetazoline increase the chance of birth defects?

Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. Oxymetazoline is not expected to increase the chance of birth defects above the background risk.

◈ Does taking oxymetazoline in pregnancy increase the chance of other pregnancy-related problems?

Studies have not been done to see if oxymetazoline increases the chance for pregnancy-related problems such as preterm delivery (birth before week 37) or low birth weight (weighing less than 5 pounds, 8 ounces [2500 grams] at birth).A report of 12 pregnancies in healthy people exposed to a one-time nasal spray dose of oxymetazoline showed no effect on uterine blood flow.

◈ Does taking oxymetazoline in pregnancy affect future behavior or learning for the child?

Studies have not been done to see if oxymetazoline can cause behavior or learning issues for the child.

◈ Breastfeeding while taking oxymetazoline:

Oxymetazoline has not been well-studied for use while breastfeeding. Since oxymetazoline is sprayed into the nose or rubbed onto skin, it is thought that very little of the medication passes into breastmilk. Be sure to talk to your healthcare provider about all your breastfeeding questions.

◈ If a male takes oxymetazoline, could it affect fertility (ability to get partner pregnant) or increase the chance of birth defects?

Studies have not been done to see if oxymetazoline could affect male fertility or increase the chance of birth defects above the background risk. In general, exposures that fathers or sperm donors have are unlikely to increase risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.

12.1.2 Acute Effects

12.1.3 Interactions

If significant systemic absorption of nasal /or ophthalmic/ oxymetazoline occurs, concurrent use of maprotiline or tricyclic antidepressants may potentiate the pressor effect of oxymetazoline.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2320
A case is described in which a 34 yr old man presented with severe hypertension, cardiomegaly, and congestive heart failure, presumably due to oxymetazoline hydrochloride, phenylephrine hydrochloride, and ephedrine hydrochloride, consumed in massive doses by an overuse of nasal decongestants and cough syrup. Coadamin chlorpromazine hydrochloride and trimeprazine tartrate may have contributed to the effects through anticholinergic and antihistamine properties. The patient was treated with furosemide and nifedipine. Signs and symptoms of heart failure quickly resolved and blood pressure dropped to 140/100 mm Hg. /Oxymetazoline hydrochloride/
Heyman SN, et al; DICP Ann Pharmacother 25: 1068-70 (1991)
Self-treatment of anaphylaxis due to a single 75 mg dose of ketoprofen is reported in a 39 yr old female patient who used 12 inhalations of an oxymetazoline nasal solution in each nostril to relieve the respiratory symptoms of the allergic reaction. Within min of using the nasal solution, the respiratory symptoms began to subside, and the patient slept through the night and consulted her doctor the next day.
Kim KT, et al; Lancet 341: 439 (1993)
Reported is a case of chronic hallucination in a 61-yr-old man associated with long term use of phenylephrine hydrochloride (Neo-Synephrine), and, more recently, oxymetazoline hydrochloride (Afrin) nasal preparations. Trifluoperazine hydrochloride (10 mg/day) was begun, nasal preparations were discontinued, and a combination of pseudoephedrine hydrochloride and tripolidine hydrochloride (Actifed) was given 2 times/day. The nasal obstruction gradually decreased and the symptoms of psychosis and anxiety were alleviated.
Escobar JI, Karno M; JAMA 247 (Apr 2): 1859-60 (1982)

12.1.4 Antidote and Emergency Treatment

/VET:/ Decontamination may not be practical due to the rapid absorption and onset of clinical signs. Heart rate and rhythm and blood pressure should be assessed, and an ECG obtained if needed. IV fluids should be given, along with atropine at 0.02 mg/kg, IV, if bradycardia is present. Diazepam (0.25-0.5 mg/kg, IV) can be given if CNS signs (eg, apprehension, shaking) are present. Serum electrolytes (ie, potassium, sodium, chloride) should be assessed and corrected as needed. Yohimbine, which is a specific a2-adrenergic antagonist, can also be used at 0.1 mg/kg, IV, and repeated in 2-3 hr if needed. /Imidazoline decongestants/
Kahn, C.M. (Ed.); The Merck Veterinary Manual 9th ed. Merck & Co. Whitehouse Station, NJ. 2005, p. 2526

12.1.5 Human Toxicity Excerpts

/SIGNS AND SYMPTOMS/ Excessive dosage and/or prolonged or too frequent intranasal use of oxymetazoline may irritate nasal mucosa and, especially in children, cause adverse systemic effects. Excessive dosage or inadvertent ingestion in children may cause profound CNS depression, possibly necessitating intensive supportive care. CNS depression, shock-like hypotension, and coma have occurred following overdosage of naphazoline and tetrahydrozoline; the possibility that this may occur with oxymetazoline should be considered.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 2824
/CASE REPORTS/ In this incident, oxymetazoline nasal spray 0.025% was administered to a 2-year-old patient during general anesthesia for nasal endoscopy. Severe hypertension with reflex bradycardia progressed to sinus arrest and was successfully treated with atropine and cardiopulmonary resuscitation.
Thrush DN; J Clin Anesth 7 (6): 5112-4 (1995)
/CASE REPORTS/ A patient prescribed oxymetazoline hydrochloride nasal drops presented with recurrent ventricular tachycardia of fascicular origin. Cardiac ultrasound showed a calcified lesion, presumably a fibroma arising from the interventricular septum. Fascicular tachycardia related to the lesion and provoked by the use of a sympathomimetic agent is postulated.
Khan A, Dewhurst N; Br J Clin Pract 51 (3): 192-3 (1997)
/CASE REPORTS/ Oxymetazoline is a sympathomimetic amine found in over-the-counter nasal decongestants. A case of chronic use of nasal oxymetazoline associated with thunderclap headache due to reversible segmental intracranial vasoconstriction /is reported/.
Loewen AH et al; CMAJ 171 (6): 593-4 (2004)
For more Human Toxicity Excerpts (Complete) data for OXYMETAZOLINE (11 total), please visit the HSDB record page.

12.1.6 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ ... Oxymetazoline injected icvt /intracerebroventricular injection/ into the lateral ventricle of NZW rabbits induced bilateral ocular hypotension (> 7.0 mmHg) that peaked at 2 hr. Unilateral topical application of oxymetazoline induced maximal, bilateral hypotension (> 12 mm/Hg), at 3 hr, in both the contralateral and ipsilateral eyes, that persisted more than 12 hr. ...
Campbell WR, Potter DE; J Ocul Pharmacol 10 (1): 393-402 (1994)
/LABORATORY ANIMALS: Neurotoxicity/ To determine if intrathecal oxymetazoline induces histological evidence of spinal neurotoxicity, male, Sprague-Dawley rats (300-450 g; implanted with an intrathecal catheter) were treated with intrathecal saline or 100 nmol oxymetazoline twice daily for 3 days, or 200 or 300 nmol oxymetazoline once daily for 3 days. Spantide (D-Arg1, D-Try7,9, Leu11-substance P; 0.067 nmol = 0.1 ug, 0.167 nmol = 0.25 ug or 0.334 nmol = 0.5 ug) or capsaicin (0.164 mumol = 50 ug), given as a single intrathecal injection, were used as positive controls. Animals were killed 12 hr after the last injection of saline or oxymetazoline, and 72 hr after spantide or capsaicin. Spinal cord sections (L1 and adjacent segments) were examined by light microscopy for changes in gross morphology, substance P-like immunoreactivity (SP-IR) and calcitonin gene related peptide-like immunoreactivity (CGRP-IR). All doses of intrathecal oxymetazoline produced antinociception (tail-flick ED50 = 53.7 nmol, paw pressure withdrawal ED50 = 93.3 nmol). Rectal temperature decreased by 1.5-2.4 degrees C up to 12 hr after 100 nmol of intrathecal oxymetazoline. There were no signs of inflammation or necrosis, and no detectable loss or damage to either spinal afferents or motor neurons as judged by SP-IR and CGRP-IR structures in spinal cords of oxymetazoline-treated animals (all doses) as compared to intrathecal saline controls. Spantide (0.1 ug) had no antinociceptive or neurotoxic effect; 0.25 ug induced irreversible loss of the TF reflex and transient hind limb paralysis; 0.5 microgram induced irreversible loss of TF and PP responses, permanent hind limb paralysis, bladder and bowel dysfunction. The spinal cords from these animals showed signs of extensive necrosis, cavitation, and hemorrhage in the ventral horn accompanied by a loss of CGRP-IR motor neurons. Capsaicin-treated rats exhibited a permanent loss of the TF but not the PP response and a marked reduction of SP-IR spinal afferents in the dorsal horn. It is concluded that i.t. oxymetazoline produces antinociception in the rat with no detectable spinal neurotoxicity as assessed by parameters which are sensitive to the neurotoxins, spantide and capsaicin.
Loomis CW et al; Brain Res 599 (1): 73-82 (1992)
/OTHER TOXICITY INFORMATION/ In dogs, signs of intoxication may include vomiting, bradycardia, cardiac arrhythmias, poor capillary refill time, hypotension or hypertension, panting, increased upper respiratory sounds, depression, weakness, nervousness, hyperactivity, or shaking. These signs appear within 30 min to 4 hr postexposure. In general, imidazoline decongestant exposure may affect the GI, cardiopulmonary, and nervous systems. /Imidazoline decongestions/
Kahn, C.M. (Ed.); The Merck Veterinary Manual 9th ed. Merck & Co. Whitehouse Station, NJ. 2005, p. 2526

12.1.7 Non-Human Toxicity Values

LD50 Rat oral 800 ug/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2807
LD50 Rat sc 1100 ug/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2807

12.1.8 Protein Binding

_In vitro_, oxymetazoline is 56.7% to 57.5% bound to human plasma proteins.

13 Associated Disorders and Diseases

14 Literature

14.1 Consolidated References

14.2 NLM Curated PubMed Citations

14.3 Springer Nature References

14.4 Thieme References

14.5 Wiley References

14.6 Nature Journal References

14.7 Chemical Co-Occurrences in Literature

14.8 Chemical-Gene Co-Occurrences in Literature

14.9 Chemical-Disease Co-Occurrences in Literature

15 Patents

15.1 Depositor-Supplied Patent Identifiers

15.2 WIPO PATENTSCOPE

15.3 Chemical Co-Occurrences in Patents

15.4 Chemical-Disease Co-Occurrences in Patents

15.5 Chemical-Gene Co-Occurrences in Patents

16 Interactions and Pathways

16.1 Protein Bound 3D Structures

16.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Structure Code
PDBe Conformer

16.2 Chemical-Target Interactions

16.3 Drug-Drug Interactions

17 Biological Test Results

17.1 BioAssay Results

18 Classification

18.1 MeSH Tree

18.2 NCI Thesaurus Tree

18.3 ChEBI Ontology

18.4 KEGG: ATC

18.5 KEGG: Target-based Classification of Drugs

18.6 KEGG: Risk Category of Japanese OTC Drugs

18.7 KEGG: Drug Groups

18.8 WHO ATC Classification System

18.9 FDA Pharm Classes

18.10 ChemIDplus

18.11 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

18.12 ChEMBL Target Tree

18.13 UN GHS Classification

18.14 NORMAN Suspect List Exchange Classification

18.15 CCSBase Classification

18.16 EPA DSSTox Classification

18.17 MolGenie Organic Chemistry Ontology

19 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
    Phenol, 3-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-6-(1,1-dimethylethyl)-2,4-dimethyl-
    https://services.industrialchemicals.gov.au/search-assessments/
    Phenol, 3-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-6-(1,1-dimethylethyl)-2,4-dimethyl-
    https://services.industrialchemicals.gov.au/search-inventory/
  2. CAS Common Chemistry
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    https://creativecommons.org/licenses/by-nc/4.0/
  3. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  4. DrugBank
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    https://www.drugbank.ca/legal/terms_of_use
  5. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  6. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
  7. FDA Global Substance Registration System (GSRS)
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  8. Hazardous Substances Data Bank (HSDB)
  9. Human Metabolome Database (HMDB)
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    http://www.hmdb.ca/citing
  10. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  11. ChEBI
  12. FDA Pharm Classes
    LICENSE
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  13. NCI Thesaurus (NCIt)
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    https://www.cancer.gov/policies/copyright-reuse
  14. Open Targets
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    https://platform-docs.opentargets.org/licence
  15. ChEMBL
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    http://www.ebi.ac.uk/Information/termsofuse.html
  16. ClinicalTrials.gov
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    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  17. Comparative Toxicogenomics Database (CTD)
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    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  18. Drug Gene Interaction database (DGIdb)
    LICENSE
    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
    DITHIIPIN-1,1,4,4-TETROXIDE ANALOGUE 7
    https://www.dgidb.org/drugs/iuphar.ligand:6124
  19. IUPHAR/BPS Guide to PHARMACOLOGY
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    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  20. Therapeutic Target Database (TTD)
  21. DailyMed
  22. Drugs and Lactation Database (LactMed)
  23. Mother To Baby Fact Sheets
    LICENSE
    Copyright by OTIS. This work is available under the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported license (CC BY-NC-ND 3.0).
    https://www.ncbi.nlm.nih.gov/books/about/copyright/
  24. Drugs@FDA
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  25. NORMAN Suspect List Exchange
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    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    OXYMETAZOLINE
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  26. EU Clinical Trials Register
  27. National Drug Code (NDC) Directory
    LICENSE
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  28. Japan Chemical Substance Dictionary (Nikkaji)
  29. KEGG
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    https://www.kegg.jp/kegg/legal.html
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Target-based classification of drugs
    http://www.genome.jp/kegg-bin/get_htext?br08310.keg
    Risk category of Japanese OTC drugs
    http://www.genome.jp/kegg-bin/get_htext?br08312.keg
  30. MassBank Europe
  31. Metabolomics Workbench
  32. Nature Chemical Biology
  33. NIST Mass Spectrometry Data Center
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    https://www.nist.gov/srd/public-law
  34. SpectraBase
  35. NLM RxNorm Terminology
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    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  36. WHO Anatomical Therapeutic Chemical (ATC) Classification
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    https://www.whocc.no/copyright_disclaimer/
  37. PharmGKB
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    https://www.pharmgkb.org/page/policies
  38. Pharos
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  39. Protein Data Bank in Europe (PDBe)
  40. RCSB Protein Data Bank (RCSB PDB)
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  47. PubChem
  48. GHS Classification (UNECE)
  49. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  50. PATENTSCOPE (WIPO)
CONTENTS