Multiple action agents and the eye: do they really stabilize mast cells?

Multiple action drugs, such as azelastine, epinastine, ketotifen and olopatadine, have recently been suggested to combine antihistaminic effect, mast cell stabilization and anti-inflammatory action. This pharmaceutical class is, therefore, rapidly becoming the first choice for prevention and treatment for allergic conjunctivitis. Increasing in-vitro studies have been performed to investigate the mast-cell-stabilizing effect of multiple action drugs. Most of the study results agree that these drugs are able to inhibit histamine and several neoformed mediators, including cytokines and arachidonic acid-derived products, from mast cells. However, the mechanisms of action have not yet fully been elucidated. Most of the results from clinical trials as well as the in-vivo experimental studies, including the conjunctival provocation model, support the evidence of a stabilizing effect of these drugs. Evidence of a different inhibitory effect of multiple action compounds on the pro-inflammatory mediators released from the mast cells suggests the possibility to target different phases of the allergic reaction, leading to a potential improvement in the management of allergic patients.