Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline

Oxymetazoline and xylometazoline are both used as nasal mucosa decongesting alpha-adrenoceptor agonists during a common cold. However, it is largely unknown which of the six alpha-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 alpha-adrenoceptor subtypes was studied. Furthermore, the affinity and potency of the imidazolines oxymetazoline and xylometazoline at these alpha-adrenoceptor subtypes were examined in transfected HEK293 cells. The rank order of mRNA levels of alpha-adrenoceptor subtypes in human nasal mucosa was: alpha(2A) > alpha(1A) >= alpha(2B) > alpha(1D) >= alpha(2C) >> alpha(1B). Oxymetazoline and xylometazoline exhibited in radioligand competition studies higher affinities than the catecholamines adrenaline and noradrenaline at most alpha-adrenoceptor subtypes. Compared to xylometazoline, oxymetazoline exhibited a significantly higher affinity at alpha(1A)- but a lower affinity at alpha(2B)-adrenoceptors. In functional studies in which adrenoceptor-mediated Ca2+ signals were measured, both, oxymetazoline and xylometazoline behaved at alpha(2B)-adrenoceptors as full agonists but oxymetazoline was significantly more potent than xylometazoline. Furthermore, oxymetazoline was also a partial agonist at alpha(1A)-adrenoceptors; however, its potency was relatively low and it was much lower than its affinity. The higher potency at alpha(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.