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

Drugs R D. 2018 Mar;18(1):87-90. doi: 10.1007/s40268-018-0227-y.

Abstract

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.

MeSH terms

  • Administration, Topical
  • Adrenergic alpha-Agonists / administration & dosage
  • Adrenergic alpha-Agonists / adverse effects
  • Adrenergic alpha-Agonists / pharmacology
  • Biological Assay*
  • Brimonidine Tartrate / administration & dosage
  • Brimonidine Tartrate / adverse effects*
  • Brimonidine Tartrate / pharmacology
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Heart Valves / drug effects
  • Humans
  • Oxymetazoline / administration & dosage
  • Oxymetazoline / adverse effects*
  • Oxymetazoline / pharmacology

Substances

  • Adrenergic alpha-Agonists
  • Brimonidine Tartrate
  • Oxymetazoline