Hydroxyzine Pamoate

Hydroxyzine pamoate acted as a potent inhibitor of brain mast cell activation in a rodent model of experimental allergic encephalomyelitis (EAE). The mechanism of action involved the blockade of mast cell degranulation, which prevented the release of vasoactive and proinflammatory mediators such as histamine and cytokines into the central nervous system. This inhibition significantly reduced the severity of EAE clinical symptoms and delayed disease onset.
The study further demonstrated that hydroxyzine achieved its effect through antagonism of H1 histamine receptors located on mast cells and possibly through direct membrane-stabilizing properties independent of receptor binding. By suppressing mast cell activation, hydroxyzine limited the subsequent recruitment of inflammatory cells and the disruption of the blood-brain barrier, two critical events in the pathogenesis of EAE. These findings indicated that the therapeutic action of hydroxyzine in allergic and neuroinflammatory conditions involved not merely symptomatic antihistamine activity but also a disease-modifying effect on immune cell function.

Fig. 1 Immunofluorescence light photomicrographs of thalamic mast cells at day 14 post-immunization following immunocytochemistry for FcERI. (A) Treated with CFA; (B) animals with EAE. (Dimitriadou V.; et al. 2000)