title: Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline.
abstract: Oxymetazoline and xylometazoline are both used as nasal mucosa decongesting α-adrenoceptor agonists during a common cold. However, it is largely unknown which of the six α-adrenoceptor subtypes are actually present in human nasal mucosa, which are activated by the two alpha-adrenoceptor agonists and to what extent. Therefore, mRNA expression in human nasal mucosa of the six α-adrenoceptor subtypes was studied. Furthermore, the affinity and potency of the imidazolines oxymetazoline and xylometazoline at these α-adrenoceptor subtypes were examined in transfected HEK293 cells. The rank order of mRNA levels of α-adrenoceptor subtypes in human nasal mucosa was: α(2A) > α(1A) ≥ α(2B) > α(1D) ≥ α(2C) >> α(1B) . Oxymetazoline and xylometazoline exhibited in radioligand competition studies higher affinities than the catecholamines adrenaline and noradrenaline at most α-adrenoceptor subtypes. Compared to xylometazoline, oxymetazoline exhibited a significantly higher affinity at α(1A) - but a lower affinity at α(2B) -adrenoceptors. In functional studies in which adrenoceptor-mediated Ca(2+) signals were measured, both, oxymetazoline and xylometazoline behaved at α(2B) -adrenoceptors as full agonists but oxymetazoline was significantly more potent than xylometazoline. Furthermore, oxymetazoline was also a partial agonist at α(1A) -adrenoceptors; however, its potency was relatively low and it was much lower than its affinity. The higher potency at α(2B) -adrenoceptors, i.e. at receptors highly expressed at the mRNA level in human nasal mucosa, could eventually explain why in nasal decongestants oxymetazoline can be used in lower concentrations than xylometazoline.
authors.affiliation: University of Bonn, Institute of Pharmacology and Toxicology, D-53113 Bonn, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Haenisch
authors.forename: Jutta
authors.initials: J
authors.lastname: Walstab
authors.forename: Stephan
authors.initials: S
authors.lastname: Herberhold
authors.forename: Friedrich
authors.initials: F
authors.lastname: Bootz
authors.forename: Marion
authors.initials: M
authors.lastname: Tschaikin
authors.forename: René
authors.initials: R
authors.lastname: Ramseger
authors.forename: Heinz
authors.initials: H
authors.lastname: Bönisch
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D001667:Binding, Competitive; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D010109:Oxymetazoline / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011942:Receptors, Adrenergic, alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D010109:Oxymetazoline; C009695:xylometazoline