Oxymetazoline

1491-59-4   ^{CAS NUMBER}

• Molecular FormulaC₁₆H₂₄N₂O
• Average mass260.375 Da

Oxymetazoline is a selective α₁ adrenergic receptor agonist and α₂ adrenergic receptorpartial agonist. It is a topical decongestant, used in the form of oxymetazoline hydrochloride. It was developed from xylometazoline at E. Merck Darmstadt by Fruhstorfer in 1961.^[1]Oxymetazoline is generally available as a nasal spray.

Oxymetazoline HCl; CAS 2315-02-8

Oxymetazoline hydrochloride is a vasoconstrictor. Chemically it is 3-[(4,5-dihydro-1H-imidazol-2-yl)methyl]6-(1,1,-dimethylethyl)-2,4-dimethylphenolmono-hydrochloride. Its molecular weight is 296.8 for the hydrochloride salt and 260.4 for the free base. It is freely soluble in water and ethanol and has a partition coefficient of 0.1 in octanol/water. Its structural formula is:

 

 

Medical uses

Oxymetazoline is available over-the-counter as a topical decongestant in the form of oxymetazoline hydrochloride in nasal sprays such as Afrin, Operil, Dristan, Dimetapp, oxyspray, Facimin, Nasivin, Nostrilla, Sudafed OM, Vicks Sinex, Zicam, SinuFrin, and Mucinex Full Force.^[2]

Due to its vasoconstricting properties, oxymetazoline is also used to treat nose bleeds^[3][4]and eye redness due to minor irritation (marketed as Visine L.R. in the form of eye drops).^[5]

General Information

Side effects and special considerations

Rebound congestion

It is recommended that oxymetazoline not be used for more than three days, as rebound congestion, or rhinitis medicamentosa, may occur.^[6] Patients who continue to use oxymetazoline beyond this point may become dependent on the medication to relieve their chronic congestion.

Effects of benzalkonium chloride

Some studies have found that benzalkonium chloride, a common additive to oxymetazoline nasal sprays, may damage nasal epithelia and exacerbate rhinitis medicamentosa. However, the majority of studies find benzalkonium chloride to be a safe preservative.^[7]

Use in pregnancy

The Food and Drug Administration places oxymetazoline in category C, indicating risk to the fetus cannot be ruled out. While it has been shown that a single dose does not significantly alter either maternal or fetal circulation,^[8] this subject has not been studied extensively enough to draw reliable conclusions.

Overdose

If accidentally ingested, standard methods to remove unabsorbed drugs should be considered.^{[clarification needed]} There is no specific antidote for oxymetazoline, although its pharmacological effects may be reversed by α adrenergic antagonists such as phentolamine. In the event of a possibly life-threatening overdose (such as a hypertensive crisis), benzodiazepines should be considered to decrease the likelihood of seizures and convulsions, as well as reduce anxiety and to lower blood pressure. In children, oxymetazoline may produce profound central nervous system depression due to stimulation of central α₂receptors and imidazoline receptors, much like clonidine.

Pharmacology

Mechanism of action

Oxymetazoline is a sympathomimetic that selectively agonizes α₁ and, partially, α₂ adrenergic receptors.^[9] Since vascular beds widely express α₁ receptors, the action of oxymetazoline results in vasoconstriction. In addition, the local application of the drug also results in vasoconstriction due to its action on endothelial postsynaptic α₂ receptors; systemic application of α₂ agonists, in contrast, causes vasodilation because of centrally-mediated inhibition of sympathetic tone via presynaptic α₂ receptors.^[10] Vasoconstriction of vessels results in relief of nasal congestion in two ways: first, it increases the diameter of the airway lumen; second, it reduces fluid exudation from postcapillary venules.^[11] It can reduce nasal airway resistance (NAR) up to 35.7% and nasal mucosal blood flow up to 50%.^[12]

Pharmacokinetics

Imidazolines are sympathomimetic agents, with primary effects on α adrenergic receptors and little if any effect on β adrenergic receptors. Oxymetazoline is readily absorbed orally. Effects on α receptors from systemically absorbed oxymetazoline hydrochloride may persist for up to 7 hours after a single dose. The elimination half-life in humans is 5–8 hours. It is excreted unchanged both by the kidneys (30%) and in feces (10%).

History

The oxymetazoline brand Afrin was first sold as a prescription medication in 1966. After finding substantial early success as a prescription medication, it became available as an over-the-counter drug in 1975. Schering-Plough did not engage in heavy advertising until 1986.^[13]From the late 1980s to mid 1990s, Afrin featured in many notable television advertisements. Some of these commercials showed men, women, and children using other brands of nasal sprays, and then standing upside down or hanging upside down from playground equipment to prevent their nasal spray from dripping out. This was juxtaposed with Afrin users having no problems.

Society and culture

Brand names

Brand names include Afrin, Dristan, Nasivin, Nezeril, Nostrilla, Logicin, Vicks Sinex, Visine L.R., Sudafed OM, Zicam, SinuFrin and Mucinex Sinus-Max.

 

References

Oxymetazoline

Clinical data
Trade names	Afrin, Ocuclear, Drixine
AHFS/Drugs.com	Monograph
Pregnancy category	C
Dependence liability	Moderate
Routes of administration	Intranasal
ATC code	R01AA05 (WHO) R01AB07 (WHO) (combinations), S01GA04 (WHO)
Legal status
Legal status	UK: General sales list (GSL, OTC) US: OTC
Pharmacokinetic data
Metabolism	Kidney (30%), fecal (10%)
Biological half-life	5–6 hours
Identifiers
IUPAC name[show]
CAS Number	1491-59-4
PubChem CID	4636
IUPHAR/BPS	124
DrugBank	DB00935
ChemSpider	4475
UNII	8VLN5B44ZY
KEGG	D08322
ChEBI	CHEBI:7862
ChEMBL	CHEMBL762
ECHA InfoCard	100.014.618
Chemical and physical data
Formula	C16H24N2O
Molar mass	260.375 g·mol−1
3D model (Jmol)	Interactive image
Melting point	301.5 °C (574.7 °F)
SMILES[hide] Oc1c(c(c(cc1C(C)(C)C)C)CC/2=N/CCN\2)C

/////////Oxymetazoline, оксиметазолин , أوكسيميتازولين , 羟甲唑啉 , Rhofade, oxymetazoline hydrochloride, alpha1A adrenoceptor agonist, vasoconstrictor

CC1=CC(=C(C(=C1CC2=NCCN2)C)O)C(C)(C)C.Cl