title: Anti-emetic drug maropitant induces intestinal motility disorder but not anti-inflammatory action in mice.
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.
authors.affiliation: Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Shoma
authors.initials: S
authors.lastname: Mikawa
authors.forename: Shohei
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Md Shafiqul
authors.initials: MS
authors.lastname: Islam
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kaji
authors.forename: Takahisa
authors.initials: T
authors.lastname: Murata
authors.forename: Risuke
authors.initials: R
authors.lastname: Mizuno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ozaki
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hori
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D045823:Ileus / Q000209:etiology; D007249:Inflammation / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009130:Muscle, Smooth / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D011812:Quinuclidines / Q000494:pharmacology*; D046509:Tissue Culture Techniques
chemical_list: D000932:Antiemetics; D011812:Quinuclidines; C518176:maropitant