Effect of mebeverine hydrochloride on jejunal motility and epithelial transport in the anesthetized ferret.
Previous in vitro and in vivo studies demonstrate that mebeverine, administered to isolated smooth muscle preparations or given intravenously, (i.v.), acts as an antispasmodic agent and may be useful in treating intestinal hypermotility. Whether mebeverine affects intestinal mucosal transport is, however, unknown. The aim of the present study was to characterize the effect of mebeverine on both small intestinal motor activity and electrogenic epithelial transport in the urethane anesthetized ferret. The effects of mebeverine were compared following i.v. and intrajejunal (i.j.) administration. Following both routes of drug administration mebeverine dose dependently inhibited jejunal motility, with the i.j. route being more potent. However, when administered i.v. but not i.j., the doses of mebeverine that inhibited jejunal motility also significantly reduced heart rate and arterial blood pressure. Mebeverine (0.1-10 mg/kg) administered i.v. had no significant effect on epithelial transport as measured by a change in transmural potential difference. However, when dosed i.j., mebeverine (0.1-10 mg/kg) induced a decrease in potential difference towards lower lumen negativity, which was suggestive of a decrease in fluid secretion or enhancement of absorption. In conclusion, the results confirm in vivo the antispasmodic effect of mebeverine and suggested that mebeverine can influence epithelial transport, probably in the direction of enhanced intestinal absorption.
Greenwood
B
B
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.
Mandel
K G
KG
D000758:Anesthesia; D000818:Animals; D001626:Bethanechol Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004848:Epithelium / Q000378:metabolism; D005289:Ferrets; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology*; D010627:Phenethylamines / Q000494:pharmacology*
D001626:Bethanechol Compounds; D010276:Parasympatholytics; D010627:Phenethylamines; C005096:mebeverine