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 B(4) (0.03 nmol/site). An intradermal injection of substance P (100 nmol/site) increased the cutaneous concentration of leukotriene B(4), which was not affected by bepotastine besilate (10 mg/kg, oral). Leukotriene B(4) increased Ca(2+) concentration in cultured neutrophils, which was suppressed by bepotastine besilate (1-100 microM). Leukotriene B(4) increased Ca(2+) concentration in cultured dorsal root ganglion neurons, which was also suppressed by bepotastine besilate (100 microM). The results suggest that the inhibition of the actions of leukotriene B(4) as well as histamine is involved in the anti-pruritic effect of bepotastine besilate.
Andoh
Tsugunobu
T
Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Kuraishi
Yasushi
Y
D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D007975:Leukotriene B4 / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011537:Pruritus / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013373:Substance P / Q000008:administration & dosage / Q000633:toxicity*
D006634:Histamine H1 Antagonists; D010880:Piperidines; D011725:Pyridines; D007975:Leukotriene B4; D013373:Substance P; C511534:bepotastine besilate; D002118:Calcium