In Vitro Safety Pharmacology Profiling of Topical α-Adrenergic Agonist Treatments for Erythema of Rosacea

BACKGROUND Topical α-adrenergic agonist therapy has been developed to treat the persistent erythema of rosacea patients. Brimonidine and oxymetazoline are both topical α-adrenergic agonists. OBJECTIVES The objective of this in vitro safety pharmacology study was to compare the potential safety profiles of brimonidine and oxymetazoline. METHODS Brimonidine and oxymetazoline underwent pharmacological profiling with a standard panel of 151 assays, including α-adrenergic receptors and 5-hydroxytryptamine (5-HT) receptors. A valvular interstitial cell (VIC) proliferation assay was performed with oxymetazoline hydrochloride. RESULTS Brimonidine was highly selective for the α2 adrenergic receptors, specifically α2A, whereas oxymetazoline was found to be much less selective and was highly active against a wide range of targets. Negligible activity was observed with brimonidine at the 5-HT2B receptor, whereas oxymetazoline had significant 5-HT2B receptor agonist activity and caused proliferation of mitral VICs in vitro. CONCLUSION As the 5-HT2B receptor is potentially involved in drug-induced valvulopathy, the benefit/risk ratio should be carefully considered, especially in patients with cardiovascular disease or other comorbidities.