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

Journal of Veterinary Medical Science

Hiroshi OZAKI¹  Masatoshi HORI¹  Takahisa MURATA²  Md Shafiqul ISLAM¹  Noriyuki KAJI¹  Risuke MIZUNO¹  Shohei YAMAMOTO¹  Shoma MIKAWA¹ 

[1] Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113�?8657, Japan;Department of Animal Radiology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113�?8657, Japan

关键词: inflammation;    maropitant;    neurokinin receptor 1;    peristalsis;    substance P;   

DOI  :  10.1292/jvms.15-0182

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(22)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.

【 授权许可】

Unknown