1. Academic Validation
  2. Pemirolast potently attenuates paclitaxel hypersensitivity reactions through inhibition of the release of sensory neuropeptides in rats

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

  • Neuropharmacology. 2004 May;46(6):888-94. doi: 10.1016/j.neuropharm.2003.11.018.
Yoshinori Itoh 1 Toshiaki Sendo Toshio Hirakawa Shinya Takasaki Takeshi Goromaru Hitoo Nakano Ryozo Oishi
Affiliations

Affiliation

  • 1 Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. yositou@st.hosp.kyushu-u.ac.jp
Abstract

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 H(1) blocker diphenhydramine or an H(2) blocker famotidine, but was significantly reduced by a neurokinin NK(1) antagonist LY303870 (0.5 mg/kg) and an NK(2) 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.

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