Oxymetazoline (hydrochloride) (Synonyms: SCH 9384)

Oxymetazoline is an agonist of α1- and α2-adrenergic receptors (α1- and α2-ARs; Kds = 6, 320, and 390 nM for α1A-, α1B-, and α1D-ARs, respectively, Ki = 15 nM for α2-AR). It is also an agonist of the serotonin (5-HT) receptor subtype 5-HT1 (Kds = 4.68, 25.7, and 5.01 nM for 5-HT1A, 5-HT1B, and 5-HT1D, respectively). Oxymetazoline increases intracellular calcium levels in CHO cells transfected with the α1A-AR (EC50 = 40.7 nM), but does not increase it measurably in cells transfected with the α1B- or α1D-AR (EC50s = 79.4 and 240 nM, respectively). It acts as a partial agonist of the α2-AR in isolated perfused rat heart (IC50 = 63 nM and EC50 = 13.5 nM for norepinephrine release). Oxymetazoline also acts as an agonist and antagonist of the 5-HT1C receptor in the presence of methiothepin and clonidine , respectively. In functional second messenger assays, oxymetazoline inhibits forskolin-stimulated adenylate cyclase activity (EC50s = 18.6, 24.0, and 44.7 nM in tissues expressing high levels of 5-HT1A, 5-HT1B, 5-HT1D receptors, respectively) and accumulation of inositol phosphates (EC50 = 269 nM in pig choroid plexus preparations, which highly express 5-HT1C receptors). Oxymetazoline (0.2 μg/kg) decreases nasal pressure in dogs by 6.9%. Formulations containing oxymetazoline have been used as nasal decongestants.