tropisetron and Intestinal-Pseudo-Obstruction

The mechanisms by which Dai-kenchu-to (TJ-100), a kampo medicine, enhances gastrointestinal motility was investigated using isolated guinea pig ileum. TJ-100 induced contractions accompanied by autonomous contraction at a concentration of more than 3 x 10(-4) g/ml in a dose-related manner. The TJ-100-induced ileal contraction was suppressed by atropine and tetrodotoxin, but not by hexamethonium. This effect was partially suppressed in the presence of high concentrations of ICS 205-930, a serotonin 4 (5-HT4) receptor antagonist. In addition, TJ-100 showed an acetylcholine (ACh)-releasing action in the smooth muscle tissues of ileum. These results suggest that contractile response induced by TJ-100 is partially mediated by ACh released from the cholinergic nerve endings and that 5-HT4 receptors would be involved in the effect of TJ-100.

Topics: Acetylcholine; Animals; Atropine; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Gastrointestinal Motility; Guinea Pigs; Hexamethonium; Ileum; Indoles; Intestinal Pseudo-Obstruction; Male; Medicine, Kampo; Muscle Contraction; Muscle, Smooth; Nicotinic Antagonists; Panax; Parasympatholytics; Pharmaceutical Preparations; Plant Extracts; Serotonin Antagonists; Tetrodotoxin; Tropisetron; Zanthoxylum; Zingiberaceae