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

Eur J Pharmacol. 2006 Oct 10;547(1-3):59-64. doi: 10.1016/j.ejphar.2006.07.009. Epub 2006 Jul 25.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Behavior, Animal / drug effects
  • Calcium / metabolism
  • Dose-Response Relationship, Drug
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism
  • Histamine H1 Antagonists / administration & dosage
  • Histamine H1 Antagonists / pharmacology
  • Leukotriene B4 / administration & dosage
  • Leukotriene B4 / metabolism*
  • Leukotriene B4 / toxicity
  • Male
  • Mice
  • Mice, Inbred ICR
  • Neurons / drug effects
  • Neurons / metabolism
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Piperidines / administration & dosage
  • Piperidines / pharmacology*
  • Pruritus / etiology
  • Pruritus / metabolism
  • Pruritus / prevention & control*
  • Pyridines / administration & dosage
  • Pyridines / pharmacology*
  • Skin / drug effects
  • Skin / metabolism
  • Skin / pathology
  • Substance P / administration & dosage
  • Substance P / toxicity*

Substances

  • Histamine H1 Antagonists
  • Piperidines
  • Pyridines
  • Leukotriene B4
  • Substance P
  • bepotastine besilate
  • Calcium