Studies Of Pharmacodynamics Of Tegaserod Maleate

Irritable bowel syndrome (IBS) is one of the most popular and typical functional dyspepsia (FD). IBS includes a group of functional gastrointestinal (GI) disorders in which abdominal pain or discomfort is associated with defecation or a change in bowel habits, and in which there are features of disordered defecation including urgency, diarrhea and/or constipation. More and more attention are paied by research workers because of its high incidence and wide prevalence. Tegaserod Maleate (TM) is a receptor partial agonist which binds with high affinity to 5-HT4 receptor.In this thesis we studied and analyzed the stimulative action of TM on gastrointestinal motility and the mechanisms of this action by using intact animals and isolated organs.The results showed that TM facilitated markedly gastric emptying in normal rats but had no obvious effect on gastric emptying delayed by morphine or fenfluramine in rats. TM had obvious effect on the charcoal meal transit in small intestine of normal mice and promoted significantly delayed small intestinal propulsion induced by atropine or dopamine. TM could increase the stool frequency both in normal mice and in constipation-mice induced by diphenoxylate. In the experiment on colon propulsion in guinea pigs TM increased the velocity of pellet propulsion significantly. TM increased the contraction of the isolated rat gastric fundal strip and isolated guinea-pig distal colon. TM inhibited the emesis induced by Copper Sulfate in pigeons.In summary, TM could obviously promote the motility of gastrointestinal tract. It has been suggested to be useful in constipation-predominant IBS.