Pemirolast potently attenuates paclitaxel hypersensitivity reactions through inhibition of the release of sensory neuropeptides in rats

Yoshinori Itoh, Toshiaki Sendo, Toshio Hirakawa, Shinya Takasaki, Takeshi Goromaru, Hitoo Nakano, Ryozo Oishi

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12 Citations (Scopus)


The effects of anti-allergic agents on the hypersensitivity reactions to paclitaxel, an anti-cancer agent, were examined in rats. Intravenous injection of paclitaxel (15 mg/kg) caused a marked extravasation of plasma protein in lungs and a transient decrease in arterial partial oxygen pressure (PaO 2). The paclitaxel-induced protein extravasation was inhibited by low doses (0.1-1 mg/kg) of pemirolast or high doses (30-100 mg/kg) of cromoglycate. However, ketotifen was not effective. The decrease in PaO 2 induced by paclitaxel was also significantly reversed by pemirolast. On the other hand, the paclitaxel-induced plasma extravasation was not attenuated by a histamine H1 blocker diphenhydramine or an H 2 blocker famotidine, but was significantly reduced by a neurokinin NK1 antagonist LY303870 (0.5 mg/kg) and an NK2 antagonist SR48968 (1 mg/kg). The concentrations of proteins and sensory peptides such as substance P, neurokinin A and calcitonin gene-related peptide but not histamine in the rat bronchoalveolar lavage fluid were elevated by paclitaxel injection. Both cromoglycate and pemirolast reduced the paclitaxel-induced rise in proteins and sensory peptides. Therefore, we demonstrated for the first time that sensory nerve peptides are involved in paclitaxel hypersensitivity and that an anti-allergic agent pemirolast attenuates the paclitaxel response by inhibiting the release of sensory nerve peptides.

Original languageEnglish
Pages (from-to)888-894
Number of pages7
Issue number6
Publication statusPublished - May 1 2004
Externally publishedYes



  • Hypersensitivity
  • Paclitaxel
  • Pemirolast
  • Pulmonary dysfunction
  • Sensory nerve peptides

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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