Vasoconstriction and anti-inflammatory properties of the selective α-adrenergic receptor agonist brimonidine

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 alpha(2)-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 alpha(1A), alpha(1B), alpha(2A), alpha(2B) and alpha(2C) 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 alpha(2A) adrenoreceptor (EC50 0.45 nM) over the other alpha-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 200 mu m (EC50 0.4 nM). 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. Conclusion: 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. (C) 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.