Laxative and anti-diarrheal activity of polycarbophil in mice and rats.
We investigated the laxative and anti-diarrheal activity of polycarbophil, an insoluble hydrophilic polymer, in comparison with other agents used for treating functional bowel disorder (FBD). In naive rats, polycarbophil (500 mg/kg) increased fecal weight and water contents without producing diarrhea. Carboxymethylcellulose (CMC) did not produce evident changes in bowel movement. Picosulfate markedly produced diarrhea. Loperamide, trimebutine and granisetron decreased stool output dose-dependently. Constipation, indicated by decrease in fecal weight, was produced by loperamide and clonidine in rats. Polycarbophil (500 mg/kg) and CMC increased fecal weight without diarrhea. Conversely trimebutine further decreased fecal weight in constipated rats. Polycarbophil (500 mg/kg) suppressed diarrhea induced by castor oil, and at 250-500 mg/kg, it produced shaped stools in animals with stools loosened by prostaglandin E2, serotonin or carbachol in mice. Polycarbophil (500 mg/kg) also reduced stools in rats with stool output increased by wrap restraint stress (WRS). CMC had no effect in the diarrhea models, except for carbachol-induced diarrhea, and WRS-induced evacuation. Loperamide, trimebutine and granisetron inhibited diarrhea production and WRS-induced evacuation, except for carbachol-induced diarrhea. The results show that polycarbophil prevents constipation and diarrhea without inducing diarrhea or constipation, which is different from the other agents. Hydrophilic polymers such as polycarbophil will be promising agents for the treatment of FBD.
Saito
Takaharu
T
Research and Development Headquarters, Hokuriku Seiyaku, Co., Ltd., Katsuyama, Fukui, Japan. takaharu.saito@abbott.com
Mizutani
Fujie
F
Iwanaga
Yuji
Y
Morikawa
Kouji
K
Kato
Hideo
H
D000180:Acrylic Resins / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000930:Antidiarrheals / Q000494:pharmacology* / Q000627:therapeutic use; D002217:Carbachol / Q000633:toxicity; D002368:Castor Oil / Q000633:toxicity; D002400:Cathartics / Q000494:pharmacology* / Q000627:therapeutic use; D003248:Constipation / Q000139:chemically induced / Q000188:drug therapy; D003672:Defecation / Q000187:drug effects; D003967:Diarrhea / Q000139:chemically induced / Q000188:drug therapy; D015232:Dinoprostone / Q000633:toxicity; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012701:Serotonin / Q000633:toxicity
D000180:Acrylic Resins; D000930:Antidiarrheals; D002400:Cathartics; D012701:Serotonin; D002368:Castor Oil; C030312:calcium polycarbophil; D002217:Carbachol; D015232:Dinoprostone