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.