Oxymetazoline, sold under the brand name Afrin among others, is a topical decongestant and vasoconstrictor medication. It is available over-the-counter as a nasal spray to treat nasal congestion and nosebleeds, as eyedrops to treat eye redness due to minor irritation, and (in the United States) as a prescription topical cream to treat persistent facial redness due to rosacea in adults. Its effects begin within minutes and last for up to six hours. Intranasal use for longer than three days may cause congestion to recur or worsen, resulting in physical dependence. Oxymetazoline is a derivative of imidazole. It was developed from xylometazoline at E. Merck Darmstadt by Wolfgang Fruhstorfer and Helmut Müller-Calgan in 1961. A direct sympathomimetic, oxymetazoline binds to and activates α1 adrenergic receptors and α2 adrenergic receptors, most notably. One study classified it in the following order: α(2A) > α(1A) ≥ α(2B) > α(1D) ≥ α(2C) >> α(1B), but this is not universally agreed upon. There is little consistency across the (relatively large) number of in-vitro studies with respect to binding affinity/selectivity. Medical uses Oxymetazoline is available over-the-counter as a topical decongestant in the form of oxymetazoline hydrochloride in nasal sprays. In the United States, oxymetazoline 1% cream is approved by the Food and Drug Administration for topical treatment of persistent facial erythema (redness) associated with rosacea in adults. Due to its vasoconstricting properties, oxymetazoline is also used to treat nose bleeds and eye redness due to minor irritation (marketed as Visine L.R. in the form of eye drops). In July 2020, oxymetazoline received approval by the FDA for the treatment of acquired drooping eyelid. Side effects Rebound congestion Rebound congestion, or rhinitis medicamentosa, may occur. A 2006 review of the pathology of rhinitis medicamentosa concluded that use of oxymetazoline for more than three days may result in rhinitis medicamentosa and recommended limiting use to three days. Australian regulatory submission In a submission to the Therapeutic Goods Administration, a Novartis representative concluded, "The justification was not based on evidence." Citing an existing extensive body of evidence and noting a range of recommended periods from five to ten days, Novartis recommended the established five day period for its use for self-medication without medical consultation as it coincides with the typical duration of the common cold. 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