Emedastine

Emedastine is a second generation, selective histamine H1 receptor antagonist with anti-allergic activity. Emedastine reversibly and competitively blocks histamine by binding to H1 receptors, thus blocking its downstream activity. As a result this agent interferes with mediator release from mast cells either by inhibiting calcium ion influx across mast cell/basophil plasma membrane or by inhibiting intracellular calcium ion release within the cells. In addition, emedastine may also inhibit the late-phase allergic reaction mediated through leukotrienes or prostaglandins, or by producing an anti-platelet activating factor effect. Upon ocular administration, emedastine causes a dose-dependent inhibition of histamine-stimulated vascular permeability in the conjunctiva. Emedastine does not affect adrenergic, dopamine, or serotonin receptors. (In Vitro) :Emedastine inhibits histamine H2 receptor (Ki=49067 nM) and histamine H3 receptor (Ki=12430 nM) .High concentrations of Emedastine (1 and 10 ng/ml) significantly inhibits type 1 collagen production in normal human dermalfibroblasts.Emedastine (1, 10, 100, 1000 nM) at concentrations of ≥ 10 nM inhibits CC chemokine-elicited eosinophil migration. (In Vivo) :Emedastine (0.03, 0.1, 0.3 mg/kg; orally; pretreatment of 30 min) significantly suppresses histamine-induced scratching with 0.1 and 0.3 mg/kg but not 0.03 mg/kg.Pretreatment with Emedastine (0.03, 0.1, 0.3 mg/kg; orally) significantly inhibits the scratching induced by substance P and leukotriene B.Emedastine (0.3 mg/kg, p.o.) produces significant inhibition of passive peritoneal anaphylaxis in guinea-pigs.Emedastine inhibits histamine-induced contractions of isolated ileum (IC50=6.1 nM) .