Xylometazoline

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Xylometazoline
Xylometazoline.svg
Clinical data
Pronunciation /ˌzaɪloʊˌmɛtəˈzoʊliːn/
ZY-lo-MET-ə-ZOH-leen
Trade names Otrivin, Otrivine, others
AHFS/Drugs.com Monograph
MedlinePlus a608026
License data
Dependence
liability 		Moderate [1]
Routes of
administration 		intranasal (spray or drops)
Drug class α1 and α2 Adrenergic receptor agonist,
Decongestant
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life 2–3 hours [ citation needed ]
Excretion Urinary
Identifiers
  • 2-[(4-tert-butyl-2,6-dimethylphenyl)methyl]-
    4,5-dihydro-1H-imidazole
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.007.629 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C16H24N2
Molar mass 244.382 g·mol−1
3D model (JSmol)
  • N\1=C(\NCC/1)Cc2c(cc(cc2C)C(C)(C)C)C
  • InChI=1S/C16H24N2/c1-11-8-13(16(3,4)5)9-12(2)14(11)10-15-17-6-7-18-15/h8-9H,6-7,10H2,1-5H3,(H,17,18) Yes check.svgY
  • Key:HUCJFAOMUPXHDK-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Xylometazoline, also spelled xylomethazoline, is a medication used to reduce symptoms of nasal congestion, allergic rhinitis, and sinusitis. [2] It is used directly in the nose as a spray or drops. [3]

Contents

Side effects include trouble sleeping, irritation of the nose, nausea, nosebleed (3%), period pain (10%) and headache (3%). [4] [2] [3] Long term use (> 10 days) is not recommended due to a rhinitis medicamentosa when stopped. [4] [5] Use is not recommended during pregnancy. [2] Xylometazoline is in the decongestant and alpha-adrenergic agonist families of medication. [5] [6]

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. [7]

Xylometazoline was patented in 1956 and came into medical use in 1959. [8] [9] It is on the World Health Organization's List of Essential Medicines. [10] Xylometazoline is available as a generic medication. [3]

Mechanism of action

Xylometazoline works by stimulating adrenergic receptors on the lamina propria of blood vessels 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 to be visibly paler after dosage.

Xylometazoline is an imidazole derivative which is designed to mimic the molecular shape of adrenaline. It binds to α1 and α2 adrenergic receptors [11] in the nasal mucosa. Due to its sympathomimetic effects, it should not be used by people with high blood pressure, or other heart problems.

Extended usage of xylometazoline can result in decreased effectiveness or a buildup of tolerance against the drug. [12] The number of receptors decreases, and when the administration of the drug is ceased, chronic congestion can occur; this is called rhinitis medicamentosa, commonly referred to as rebound congestion. Moreover, long-term overdosing can cause degenerative changes in nasal mucous membranes that pose another health problem.[ citation needed ]

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. [13]

Brand names

The most common name for over-the-counter products containing xylometazoline internationally is "Otrivin" (used in Australia, [14] Canada, Estonia, Finland, Greece, Hungary, India, [15] 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), Xylomet (Opsonin, Bangladesh), 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), 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) Xynosine (in Pakistan, Afghanistan, Kyrgyzstan and Kazakhstan), 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). [16]

Synthesis

5-tert-Butyl-m-xylene is reacted with chloromethyl methyl ether in the presence of zinc chloride to form 2,6-dimethyl-4-tert-butyl-benzylchloride, which is then reacted with sodium cyanide in the presence of potassium iodide 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. [17] Carbon disulfide can also be used as a catalyst in the last step. [18] When using para-toluenesulfonic acid, the resulting salt can be basified and extracted with hydrochloric acid to produce xylometazoline hydrochloride, which is the main form used in medications.

References

  1. ↑ Fulga A, Zenovia A, Ene DC, Stan C, Firescu D, Fulga I (18 November 2021). "Fulga, Ana, Andrei Zenovia, Doriana Cristea Ene, Constantin Stan, Dorel Firescu, and Iuliu Fulga. 2021. "Addiction to Nasal Decongestants Based on Α-Adrenoceptor Agonists Case Series and Literature Review: Array". EuroEconomica 40 (2)". Euroeconomica. 40 (2).
  2. 1 2 3 "Otrivine Adult Measured Dose Sinusitis Spray - Summary of Product Characteristics (SPC) - (eMC)". www.medicines.org.uk. 13 April 2016. Archived from the original on 29 December 2016. Retrieved 28 December 2016.
  3. 1 2 3 British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 786. ISBN   978-0-85711-156-2.
  4. 1 2 Eccles R, Martensson K, Chen SC (April 2010). "Effects of intranasal xylometazoline, alone or in combination with ipratropium, in patients with common cold". Current Medical Research and Opinion. 26 (4): 889–899. doi:10.1185/03007991003648015. PMID   20151787. S2CID   34728458.
  5. 1 2 Graf P (1997). "Rhinitis medicamentosa: aspects of pathophysiology and treatment". Allergy. 52 (40 Suppl): 28–34. doi:10.1111/j.1398-9995.1997.tb04881.x. PMID   9353558. S2CID   72326981.
  6. ↑ "Xylometazoline nasal medical facts from Drugs.com". www.drugs.com. Archived from the original on 29 December 2016. Retrieved 28 December 2016.
  7. ↑ Proudman RG, Akinaga J, Baker JG (October 2022). "The signaling and selectivity of α-adrenoceptor agonists for the human α2A, α2B and α2C-adrenoceptors and comparison with human α1 and β-adrenoceptors". Pharmacology Research & Perspectives. 10 (5): e01003. doi:10.1002/prp2.1003. PMC   9471048 . PMID   36101495.
  8. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 552. ISBN   978-3-527-60749-5. Archived from the original on 29 December 2016.
  9. ↑ USpatent 2868802A,Hüni, Albrecht,"2-(γ-TERT-BUTYL-O,O'-DIMETHYL-PHENYL-METHYL)-IMIDAZOLINE AND SALTS",issued 1959-01-13, assigned to Ciba Pharmaceutical Products Inc., Summit, N. J.
  10. ↑ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl: 10665/371090 . WHO/MHP/HPS/EML/2023.02.
  11. ↑ Haenisch B, Walstab J, Herberhold S, Bootz F, Tschaikin M, Ramseger R, et al. (December 2010). "Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline". Fundamental & Clinical Pharmacology. 24 (6): 729–739. doi:10.1111/j.1472-8206.2009.00805.x. PMID   20030735. S2CID   25064699.
  12. ↑ Gold Standard Clinical Pharmacology Archived 2008-05-25 at the Wayback Machine
  13. ↑ "FDA Drug Safety Communication: Serious adverse events from accidental ingestion by children of over-the-counter eye drops and nasal sprays". FDA. July 2021.
  14. ↑ "xylometazoline". Healthdirect Australia. Retrieved 25 October 2019.
  15. ↑ "Otrivin | GSK Consumer Healthcare INDIA" . Retrieved 17 June 2018.
  16. ↑ "Xylometazoline nasal Uses, Side Effects & Warnings". Archived from the original on 22 February 2015. Retrieved 22 February 2015.
  17. ↑ "Synthetic method of xylometazoline hydrochloride compound". Google Patents. 19 September 2010. Retrieved 20 January 2025.
  18. ↑ Golander Y, DeWitte WJ (1985). "Xylometazoline Hydrochloride". Analytical Profiles of Drug Substances. Vol. 14. Elsevier. pp. 135–156. doi:10.1016/s0099-5428(08)60579-1. ISBN   978-0-12-260814-8.
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