Emedastine (fumarate)

Emedastine is a potent and selective histamine H1 receptor antagonist with 37,744-fold and 9,562-fold selectivity over H2 and H3, respectively (Kis = 1.3, 49,067, and 12,430 nM for H1, H2, and H3, respectively). It is selective for H1 receptors with less than 50% inhibition of α1-, α2-, and β1-adrenergic, dopamine D1 and D2, and serotonin 5-HT1 and 5-HT2 receptors at a concentration of 10 µM. It inhibits histamine-induced phosphoinositide turnover and intracellular calcium mobilization in primary human conjunctival epithelial cells (HCECs; IC50s = 1.6 and 2.9 nM, respectively). Emedastine inhibits histamine-stimulated cytokine secretion by primary HCECs, including IL-6, IL-8, and GM-CSF secretion (IC50s = 2.23, 3.42, and 1.50 nM, respectively). In guinea pigs, ocular application of emedastine 4 hours after histamine challenge inhibits vascular permeability with an ED50 value of 0.019% w/v. Formulations containing emedastine have been used in the treatment of allergic conjunctivitis.