Olopatadine

Histamine is a biogenic vasoactive amine that binds to its receptors, which are G-protein coupled receptors. Signaling through the histamine H1 receptor is thought to primarily promote the activation of inflammatory reactions, such as allergy, asthma, and autoimmune diseases. H1 receptor signaling activates the intracellular transcription factors, such as IP3, PLC, PKC, DAG, and intracellular calcium ions, which all work to activate further downstream cascades. Activated downstream cascades lead to the production of cytokines, the release of mast cell inflammatory mediators, synthesis of prostacyclins, activation of platelet factor, as well as the synthesis of nitric oxide, arachidonic acid, and thromboxane, which all contribute to inflammatory reactions.

Olopatadine is an anti-allergic molecule that works via several mechanisms. As a mast cell stabilizer, it stabilizes rodent basophils and human conjunctival mast cells and inhibits the immunologically-stimulated release of histamine. Olopatadine acts as an antagonist at the histamine H1 receptors with high selectivity, which is explained by a unique receptor binding pocket that consists of the aspartate residue in the third transmembrane helix and other sites in the H1 receptor. Upon binding, olopatadine blocks the H1 receptor signaling pathway, inhibiting the release of inflammatory mediators, such as tryptase, prostaglandin D2, TNF-alpha, as well as pro-inflammatory cytokines. It also decreases chemotaxis and inhibits eosinophil activation. In vitro, olopatadine was shown to inhibit epithelial cell intercellular adhesion molecule-1 (ICAM-1), which promotes the recruitment of migrating pro-inflammatory mediators.