Anti-emetic drug maropitant induces intestinal motility disorder but not
anti-inflammatory action in mice |
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| Authors: | Shoma MIKAWA Shohei YAMAMOTO Md Shafiqul ISLAM Noriyuki KAJI Takahisa MURATA Risuke MIZUNO Hiroshi OZAKI Masatoshi HORI |
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| Institution: | 1)Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113–8657, Japan;2)Department of Animal Radiology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113–8657, Japan |
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| 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. Ex vivo examination of
luminal pressure-induced intestinal motility of whole intestine revealed that maropitant
(0.1–10 µM) increased frequency of contraction, decreased amplitude of
contraction and totally inhibited motility index in a concentration-dependent manner. We
measured intestinal transit in vivo 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 in vivo. |
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| Keywords: | inflammation maropitant neurokinin receptor 1 peristalsis substance P |
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