sincalide and Diarrhea

Topics: Analgesics, Opioid; Colonic Diseases, Functional; Constipation; Diarrhea; Diverticulum, Colon; Electromyography; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Manometry; Parasympatholytics; Prostaglandins; Receptors, Cholecystokinin; Serotonin Antagonists; Sincalide; Somatostatin

Although colon dysmotility is recognized as a pathophysiological factor in irritable bowel syndrome (IBS), it has not been characterized. We have investigated motility patterns in IBS patients with abdominal pain and frequent defecation or diarrhea and in healthy volunteers.. A recording catheter that had six polyvinyl tubes with infusion ports was placed in the transverse, descending, and sigmoid colon under fluoroscopy. After 2-h basal recordings, motility responses to cholecystokinin octapeptide (CCK-8) and a meal were studied for 3 h. The motility index (MI) and number of high amplitude propagating contractions (HAPCs) in 10 IBS patients were compared with those of 10 controls. HAPCs were correlated with abdominal pain, and colon transit time using radio-opaque markers was determined. Using human colon muscle strips, the effect of CCK-8 on muscle contractions was also studied.. The MI and mean number and peak amplitude of HAPCs in IBS patients were significantly greater than in controls. These abnormalities paralleled markedly shortened colonic transit time. Abdominal pain coincided with >90% of HAPCs. Dose-dependent muscle contraction by CCK-8 was profoundly suppressed both by loxiglumide and atropine.. The dysmotility in this subset of IBS patients was characterized by significantly increased occurrences of powerful HAPCs that paralleled rapid colon transit and were accompanied by abdominal pain. Thus, it is suggested that this powerful contraction is one of the causes of abdominal pain. The action of CCK-8 seems to be mediated via the colon enteric nervous system.

Topics: Abdominal Pain; Adult; Aged; Colon; Colonic Diseases, Functional; Diarrhea; Fasting; Female; Gastrointestinal Motility; Gastrointestinal Transit; Humans; In Vitro Techniques; Male; Middle Aged; Muscle, Smooth; Postprandial Period; Reference Values; Sincalide

Tiropramide hydrochloride and some of its metabolites were studied in vivo for their antispasmodic activities on the following models: gastric emptying in the mouse retarded by cholecystokinin octapeptide (CCK-8) or morphine, progression of intestinal contents in the mouse, spontaneous motility of the colon in the anesthetized rabbit, diarrhea induced by castor oil in the rat, spasm of the sphincter of Oddi provoked by morphine in the guinea pig, contractions of the urinary bladder in the anesthetized rat. On these models tiropramide had an antispasmodic activity at doses of 4-40 mg/kg i.p. or i.v. and of 50-90 mg/kg orally. The potency was greater on "pathological" contractions or spasms and smaller on "physiological" movements. Tiropramide may therefore be regarded as a "eukinetic" antispasmodic agent. Tiropramide in general was more potent than reference agents such as papaverine or flavoxate and was active also after oral administration. The metabolites of tiropramide, i.e. CR 1034, CR 1098 and CR 1166 showed similar pharmacodynamic effects, but their potency was smaller than that of tiropramide. Large doses of tiropramide have depressive actions on the cardiovascular system, which can be seen especially if tiropramide is administered i.v. and are less pronounced after oral administration. The circulatory effects are therefore probably the limiting factor for increasing the parenteral doses of tiropramide in human therapy. Tiropramide was found less toxic than papaverine (LD50). The metabolites of tiropramide were less toxic than the parent compound. The toxicity of the chiralic forms of tiropramide does not differ significantly from that of the racemic substance.

Topics: Animals; Diarrhea; Dogs; Female; Gastric Emptying; Gastrointestinal Motility; Guinea Pigs; Hemodynamics; Humans; Intestinal Mucosa; Male; Mice; Morphine; Parasympatholytics; Rabbits; Rats; Rats, Inbred Strains; Respiration; Sincalide; Sphincter of Oddi; Tyrosine; Urinary Bladder

We compared responses of the gallbladder to graded intravenous infusions of cholecystokinin octapeptide (CCK-OP) in normal controls (n = 8) and patients with irritable bowel syndrome (IBS) with predominant constipation (n = 8) or diarrhea (n = 8). The doses of CCK-OP ranged from subphysiological (negligible contraction of the gallbladder) to supraphysiological (90% contraction of gallbladder and abdominal side effects) amounts. All gallbladders contracted progressively in response to CCK-OP, and a Weibull model (power exponential function) described precisely the gallbladder's response to CCK-OP. Patients with IBS responded differently from normal patients; those with constipation contracted their gallbladders more and those with diarrhea contracted less in response to the peptide. Gallbladders were also stimulated with a high-fat, liquid meal; all patients' gallbladders contracted, but clear differences between groups could not be demonstrated postprandially. The results suggest that the smooth muscle of the gallbladder in IBS has an abnormal sensitivity to CCK-OP, and the results support the concept that IBS can be a generalized abnormality of the smooth muscle of the digestive tract.

Topics: Adult; Colonic Diseases, Functional; Constipation; Diarrhea; Dietary Fats; Female; Gallbladder; Humans; Male; Muscle Contraction; Muscle, Smooth; Sincalide; Ultrasonography