Suppression by bepotastine besilate of substance P-induced itch-associated responses through the inhibition of the leukotriene B4 action in mice

Anti-pruritic effects of the antihistamine bepotastine besilate were studied in mice. Bepotastine besilate (10 mg/kg) inhibited scratching induced by an intradermal injection of histamine (100 nmol/site), but not serotonin (100 nmol/site). Bepotastine besilate (1–10 mg/kg, oral) dose-dependently suppressed scratching induced by substance P (100 nmol/site) and leukotriene B4 (0.03 nmol/site). An intradermal injection of substance P (100 nmol/site) increased the cutaneous concentration of leukotriene B4, which was not affected by bepotastine besilate (10 mg/kg, oral). Leukotriene B4 increased Ca2+ concentration in cultured neutrophils, which was suppressed by bepotastine besilate (1–100 μM). Leukotriene B4 increased Ca2+ concentration in cultured dorsal root ganglion neurons, which was also suppressed by bepotastine besilate (100 μM). The results suggest that the inhibition of the actions of leukotriene B4 as well as histamine is involved in the anti-pruritic effect of bepotastine besilate.