title: Vasoconstriction and anti-inflammatory properties of the selective α-adrenergic receptor agonist brimonidine.
abstract: BACKGROUND
  The facial erythema of rosacea is recognized as the most prevalent and most difficult manifestation of rosacea to treat. A recent approach in patients with rosacea has been to reduce this erythema through vasoconstriction of cutaneous blood vessels by selectively targeting α2-adrenergic receptors with brimonidine.
  
  
  OBJECTIVE
  To further investigate the pharmacodynamic profile of brimonidine, its vasoconstrictive effects and its anti-inflammatory properties.
  
  
  METHODS
  The potency for the α1A, α1B, α2A, α2B and α2C receptors of brimonidine was measured, as well as performing a large target profiling study in order to determine the target selectivity profile of brimonidine. The vasoconstrictive effects of brimonidine were measured using ex vivo wire myography and human skin biopsy neuroinflammation models. The anti-inflammatory properties of brimonidine were measured using two in vivo mice ear inflammation models.
  
  
  RESULTS
  Brimonidine was found to be highly selective for the α2A adrenoreceptor (EC50 0.45nM) over the other α-adrenoreceptors. Additionally, the large target profiling study demonstrated the high selectivity of brimonidine with minimal off-target effects. The ex vivo wire myography model showed that brimonidine is a potent vasoconstrictor of human subcutaneous vessels with a diameter of less than 200μm (EC50 0.4nM). The ex vivo human skin biopsy neuroinflammation model demonstrated that brimonidine completely inhibited vasodilation induced by capsaicin. Both in vivo mouse ear inflammation models highlighted that brimonidine inhibited ear edema (up to 76%) when compared to vehicle.
  
  
  CONCLUSIONS
  The selectivity, vasoconstrictive and anti-inflammatory properties of brimonidine that have been described in these studies are in agreement with the benefits observed with this compound in the treatment of facial erythema in rosacea.
authors.affiliation: Research, Galderma, Sophia Antipolis, France. Electronic address: David.Piwnica@galderma.com.
authors.forename: David
authors.initials: D
authors.lastname: Piwnica
authors.affiliation: Research, Galderma, Sophia Antipolis, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Rosignoli
authors.affiliation: Research, Galderma, Sophia Antipolis, France.
authors.forename: Séverine Thibaut
authors.initials: ST
authors.lastname: de Ménonville
authors.affiliation: Research, Galderma, Sophia Antipolis, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Alvarez
authors.affiliation: Research, Galderma, Sophia Antipolis, France.
authors.forename: Marlene
authors.initials: M
authors.lastname: Schuppli Nollet
authors.affiliation: Research, Galderma, Sophia Antipolis, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Roye
authors.affiliation: Research, Galderma, Sophia Antipolis, France.
authors.forename: André
authors.initials: A
authors.lastname: Jomard
authors.affiliation: Research, Galderma, Sophia Antipolis, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Aubert
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001706:Biopsy; D000068438:Brimonidine Tartrate; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008807:Mice, Inbred BALB C; D011810:Quinoxalines / Q000494:pharmacology*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000378:metabolism; D012867:Skin / Q000098:blood supply*; D046509:Tissue Culture Techniques; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000893:Anti-Inflammatory Agents; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D014662:Vasoconstrictor Agents; D000068438:Brimonidine Tartrate
keywords: Brimonidine; Inflammation; Mirvaso; Pharmacology; Rosacea; Vascular