Xylometazoline, also spelled xylomethazoline, is a

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

used to reduce symptoms of

nasal congestion Nasal congestion is the partial or complete blockage of nasal passages, leading to impaired nasal breathing, usually due to membranes lining the nose becoming swollen from inflammation of blood vessels. Background In about 85% of cases, nasal ...

allergic rhinitis Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. It is classified as a type I hypersensitivity reaction. Signs a ...

, and

sinusitis Sinusitis, also known as rhinosinusitis, is an inflammation of the mucous membranes that line the sinuses resulting in symptoms that may include production of thick nasal mucus, nasal congestion, facial congestion, facial pain, facial pressure ...

. It is used directly in the

nose A nose is a sensory organ and respiratory structure in vertebrates. It consists of a nasal cavity inside the head, and an external nose on the face. The external nose houses the nostrils, or nares, a pair of tubes providing airflow through the ...

as a spray or drops. Side effects include trouble sleeping, irritation of the nose, nausea, nosebleed (3%), period pain (10%) and headache (3%). Long term use (> 10 days) is not recommended due to a

rhinitis medicamentosa Rhinitis medicamentosa (or RM, also known as rebound congestion) is a condition of rebound nasal congestion suspected to be brought on by extended use of topical decongestants (e.g., oxymetazoline, phenylephrine, xylometazoline, and naphazoli ...

when stopped. Use is not recommended during

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

. Xylometazoline is in the

decongestant A decongestant, or nasal decongestant, is a type of pharmaceutical drug that is used to relieve nasal congestion in the upper respiratory tract. The active ingredient in most decongestants is either pseudoephedrine or phenylephrine (the latter o ...

and alpha-adrenergic agonist families of medication. One study classified it with selectivity ratios in alpha 2 adrenergic receptors of 151 for a2A vs a2B, 4.5 a2A vs a2C, and 33.9 a2B vs a2C. Making it a highly selective a2A agonist. Xylometazoline was patented in 1956 and came into medical use in 1959. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. Xylometazoline is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

Mechanism of action

Xylometazoline works by stimulating

adrenergic receptors The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like be ...

on the

lamina propria The lamina propria is a thin layer of connective tissue that forms part of the moist linings known as mucous membranes or mucosae, which line various tubes in the body, such as the respiratory tract, the gastrointestinal tract, and the urogenital ...

blood vessel Blood vessels are the tubular structures of a circulatory system that transport blood throughout many Animal, animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the Tissue (biology), tissues of a Body (bi ...

s in the nose. The decongestant effect is due to constriction of large veins in the nose which swell up during the inflammation of any infection or allergy of the nose. The smaller arteries are also constricted and this causes the colour of the nasal

epithelium Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

to be visibly paler after dosage. Xylometazoline is an

imidazole Imidazole (ImH) is an organic compound with the formula . It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. It can be classified as a heterocycle, specifically as a diazole. Many natural products, ...

derivative which is designed to mimic the molecular shape of

adrenaline Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...

. It binds to α₁ and α₂ adrenergic receptors in the nasal mucosa. Due to its sympathomimetic effects, it should not be used by people with high

blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...

, or other

heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...

problems. Extended usage of xylometazoline can result in decreased effectiveness or a buildup of tolerance against the drug. The number of receptors decreases, and when the administration of the drug is ceased, chronic congestion can occur; this is called

, commonly referred to as rebound congestion. Moreover, long-term overdosing can cause degenerative changes in nasal

mucous membrane A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It ...

s that pose another health problem.

Society and culture

In 2021, a US FDA Drug Safety Communication stated that, while a US Consumer Product Safety Commission (CPSC) proposed rule regarding child-resistant packaging covered products containing xylometazoline, no such products were marketed in the United States at that time.

Brand names

The most common name for over-the-counter products containing xylometazoline internationally is "Otrivin" (used in Australia, Canada, Estonia, Finland, Greece, Hungary, India, Israel, Jordan, Netherlands, New Zealand, Norway, Poland, South Africa, Egypt, Sweden, Vietnam, Hong Kong), "Otrivine" (United Kingdom, Ireland, Turkey, Belgium), or "Otriven" (Germany). A product marketed as "Otrivin Oxy" contains oxymetazoline instead of xylometazoline. Other product names used include Antazol (Square, in

Bangladesh Bangladesh, officially the People's Republic of Bangladesh, is a country in South Asia. It is the List of countries and dependencies by population, eighth-most populous country in the world and among the List of countries and dependencies by ...

), Xylomet (Opsonin,

), Cirovin, Klarigen (in Denmark), Nasolin (in Finland), Neo-Rinoleina, Novorin, Olynth, Otrinoz, Galazolin (Russia, Ukraine, Belarus), Nasomist-X, Otrix, Rhinoset, Zenfresh, Naphthyzinium, Xymelyn (in

Latvia Latvia, officially the Republic of Latvia, is a country in the Baltic region of Northern Europe. It is one of the three Baltic states, along with Estonia to the north and Lithuania to the south. It borders Russia to the east and Belarus to t ...

), Sinutab Nasal Spray, Snup akut, Sudafed, Xylo-COMOD, Xylolin (in the United Arab Emirates), Xylovit, Olynth (in Serbia, the Czech Republic, Lithuania and Slovakia), Meralys (in

Croatia Croatia, officially the Republic of Croatia, is a country in Central Europe, Central and Southeast Europe, on the coast of the Adriatic Sea. It borders Slovenia to the northwest, Hungary to the northeast, Serbia to the east, Bosnia and Herze ...

) Xynosine (in

Pakistan Pakistan, officially the Islamic Republic of Pakistan, is a country in South Asia. It is the List of countries and dependencies by population, fifth-most populous country, with a population of over 241.5 million, having the Islam by country# ...

Afghanistan Afghanistan, officially the Islamic Emirate of Afghanistan, is a landlocked country located at the crossroads of Central Asia and South Asia. It is bordered by Pakistan to the Durand Line, east and south, Iran to the Afghanistan–Iran borde ...

Kyrgyzstan Kyrgyzstan, officially the Kyrgyz Republic, is a landlocked country in Central Asia lying in the Tian Shan and Pamir Mountains, Pamir mountain ranges. Bishkek is the Capital city, capital and List of cities in Kyrgyzstan, largest city. Kyrgyz ...

and

Kazakhstan Kazakhstan, officially the Republic of Kazakhstan, is a landlocked country primarily in Central Asia, with a European Kazakhstan, small portion in Eastern Europe. It borders Russia to the Kazakhstan–Russia border, north and west, China to th ...

), Xymelin, Zymelin, Xylostar, Xylorin (in Poland), Nasobol, Xylo Mepha and others (Switzerland), Decozal (in Jordan), Nasic, Orinox (Romania), Narhimed (Italy), nasa Rhinathiol (Belgium), Zolinol, Nasorhinathiol, and Vibrocil (Portugal).

Formulations

The standard adult solution strength is 0.1% w/v xylometazoline (or 1 mg per 1 mL solution).

Synthesis

5-tert-Butyl-m-xylene is reacted with chloromethyl methyl ether in the presence of

zinc chloride Zinc chloride is an Inorganic chemistry, inorganic chemical compound with the chemical formula, formula ZnCl2·''n''H2O, with ''n'' ranging from 0 to 4.5, forming water of hydration, hydrates. Zinc chloride, anhydrous and its hydrates, are colo ...

to form 2,6-dimethyl-4-tert-butyl-benzylchloride, which is then reacted with

sodium cyanide Sodium cyanide is a compound with the formula Na C N and the structure . It is a white, water-soluble solid. Cyanide has a high affinity for metals, which leads to the high toxicity of this salt. Its main application, in gold mining, also expl ...

in the presence of

potassium iodide Potassium iodide is a chemical compound, medication, and dietary supplement. It is a medication used for treating hyperthyroidism, in radiation emergencies, and for protecting the thyroid gland when certain types of radiopharmaceuticals are u ...

to produce 2,6-dimethyl-4-tert-butyl-benzylcyanide. This is then reacted with ethylene diamine in the presence of para-toluenesulfonic acid to form the corresponding imidazoline, this being xylometazoline.

Carbon disulfide Carbon disulfide (also spelled as carbon disulphide) is an inorganic compound with the chemical formula and structure . It is also considered as the anhydride of thiocarbonic acid. It is a colorless, flammable, neurotoxic liquid that is used as ...

can also be used as a

catalyst Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...

in the last step. When using para-toluenesulfonic acid, the resulting salt can be basified and extracted with

hydrochloric acid Hydrochloric acid, also known as muriatic acid or spirits of salt, is an aqueous solution of hydrogen chloride (HCl). It is a colorless solution with a distinctive pungency, pungent smell. It is classified as a acid strength, strong acid. It is ...

to produce xylometazoline hydrochloride, which is the main form used in medications.

References

{{Authority control Alpha-1 adrenergic receptor agonists Alpha-2 adrenergic receptor agonists Imidazolines Tert-butyl compounds Topical decongestants Vasoconstrictors World Health Organization essential medicines Wikipedia medicine articles ready to translate