Anti-emetic drug maropitant induces intestinal motility disorder but not anti-inflammatory action in mice

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Author(s)

    • MIKAWA Shoma MIKAWA Shoma
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113–8657, Japan
    • YAMAMOTO Shohei YAMAMOTO Shohei
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113–8657, Japan
    • KAJI Noriyuki
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113–8657, Japan
    • MURATA Takahisa
    • Department of Animal Radiology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113–8657, Japan
    • MIZUNO Risuke
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113–8657, Japan
    • OZAKI Hiroshi
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113–8657, Japan
    • HORI Masatoshi
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113–8657, Japan

Abstract

Maropitant is a neurokinin 1 receptor (NK1R) antagonist that is clinically used as a new anti-emetic drug for dogs. Substance P (SP) and its receptor NK1R are considered to modulate gastrointestinal peristalsis. In addition, SP works as an inflammatory mediator in gastrointestinal diseases. Aim of this study is to clarify the effects of maropitant on intestinal motility and inflammation in mice. <i>Ex vivo</i> examination of luminal pressure-induced intestinal motility of whole intestine revealed that maropitant (0.1–10 <i>µ</i>M) increased frequency of contraction, decreased amplitude of contraction and totally inhibited motility index in a concentration-dependent manner. We measured intestinal transit <i>in vivo</i> by measuring transportation of orally administered luminal content labeled with phenol red. Our results demonstrated that maropitant (10 mg/kg, SC) delayed intestinal transit. Geometric center value was significantly decreased in maropitant-treated mice. Anti-inflammatory effects of maropitant against leukocytes infiltration into the intestinal smooth muscle layer in post-operative ileus (POI) model mice were measured by immunohistochemistry. In POI model mice, a great number of CD68-positive macrophages or MPO-stained neutrophils infiltrated into the inflamed muscle region of the intestine. However, in the maropitant treated mice, the infiltration of leukocytes was not inhibited. The results indicated that maropitant has ability to induce disorder of intestinal motility in mice, but has no anti-inflammatory action in the mouse of a POI model. In conclusion, in mice, maropitant induces disorder of intestinal motility <i>in vivo</i>.

Journal

  • Journal of Veterinary Medical Science

    Journal of Veterinary Medical Science 77(10), 1195-1199, 2015

    JAPANESE SOCIETY OF VETERINARY SCIENCE

Codes

  • NII Article ID (NAID)
    130005107606
  • NII NACSIS-CAT ID (NCID)
    AA10796138
  • Text Lang
    ENG
  • ISSN
    0916-7250
  • NDL Article ID
    026822083
  • NDL Call No.
    Z18-350
  • Data Source
    NDL  J-STAGE 
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