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 α(2) adrenergic receptors, specifically α(2A), 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-HT(2B) receptor, whereas oxymetazoline had significant 5-HT(2B) receptor agonist activity and caused proliferation of mitral VICs in vitro. CONCLUSION: As the 5-HT(2B) 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.