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At least 1,207 records · Page 67Linked to original sources
PubMed2002

Tegaserod: a new 5-HT4 agonist.

Tegaserod is a medication that has been shown to be of benefit in women with irritable bowel syndrome (IBS) associated with abdominal pain, bloating, and constipation. Tegaserod is a selective serotonin receptor subtype 4 partial agonist designed to interact with the network of cells and nerves throughout the gastrointestinal tract that use serotonin. Tegaserod has been shown to modulate both gastrointestinal motility and visceral sensitivity. Specifically, it increases the peristaltic reflex and decreases visceral sensitivity. Clinical studies have shown that tegaserod improves symptoms of abdominal pain, bloating, and constipation in women with IBS. This article discusses the role of serotonin in gastrointestinal tract physiology, the structure and pharmacokinetic profile of tegaserod, and clinical applications of this new drug.

Abdominal Pain↗
PubMed1980

Non-ganglionic cholinergic excitatory pathways in the sympathetic supply to the feline stomach. An efferent system or afferents with excitatory axon collaterals?

Experiments were performed on chloralosed, adrenalectomized cats, paralysed with gallamine and artificially ventilated. Gastric motility was recorded by the balloon method. Efferent stimulation of the cut greater splanchnic nerve, well proximal to the celiac ganglion, could either increase or decrease gastric tone. The excitatory responses called for higher stimulation intensities than the inhibitory ones but were as a rule observed at lower frequencies only (1-4 Hz). They could be abolished by atropine but were not prevented by bilateral vagotomy, hexamethonium nor guanethidine. The latter two drugs rather reversed inhibitory responses to excitatory ones which exhibited a hyperbolic frequency-response relationship with maximal effects already at 2-4 Hz. Heating of a nerve trunk selectively activates thin afferents of the delta group and C-class. Heating of the greater splanchnic nerve caused an increase in gastric motility which, like that caused by electric stimulation, was not prevented by hexamethonium nor guanethidine; nor was it eliminated by cutting the nerve centrally, nor by vagotomy, while it was abolished by atropine. These results suggest that the excitatory gastric responses to efferent splanchnic nerve stimulation are due to antidromic activation of thin afferent fibres. Their functional significance remains obscure but their peripheral arborizations may convey 'axon reflexes' influencing gastrointestinal motility.

Afferent Pathways↗
PubMed1994

The kappa agonist fedotozine modulates colonic distention-induced inhibition of gastric motility and emptying in dogs.

BACKGROUND/AIMS: Gastric motor disturbances, associated with a delay in gastric emptying, occur in patients with the irritable bowel syndrome. The influence of fedotozine and kappa agonists on the cologastric reflex produced by nonpainful colonic distention was evaluated in conscious dogs. METHODS: Colonic distention was applied in dogs fitted with either strain gauges or gastric cannula to assess its influence on gastrointestinal motility and gastric emptying, respectively. RESULTS: Colonic distention delayed the occurrence of gastric migrating motor complex by 141%, an effect blocked by intravenous fedotozine, U 50,488 (25 and 50 micrograms/kg), and hexamethonium (0.5 mg/kg) but not by D-Ala2, N-methyl, Phe4, Gly5-ol enkephalin (1, 5, and 10 micrograms/kg), granisetron (50 and 100 micrograms/kg), or bretylium tosylate (5 mg/kg). Nor-binaltorphimine hydrochloride (1 mg/kg intravenously) eliminated the suppressive action of fedotozine. Colonic distention reduced the 1-hour gastric emptying of solids by 40.1%, an effect blocked by fedotozine and U 50,488 (50 and 100 micrograms/kg); nor-binaltorphimine hydrochloride (1 mg/kg) antagonized the blocking effect of fedotozine. CONCLUSIONS: Fedotozine acts through kappa receptors to block the colonic distention-induced delay on gastric motility and emptying. The cologastric reflex involves nicotinic ganglionic receptors but not adrenergic pathway and 5-hydroxytryptamine 3 receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2001

Development of a novel intestinal and vascular access port (IVAP) rabbit model to study regiospecific oral absorption pharmacokinetics.

BACKGROUND AND PURPOSE: The limited availability and cost of many drugs prohibits routine use of the previously developed intestinal and vascular access port (IVAP) canine model by our group. A lower animal species model such as the rabbit is suitable for implanting intestinal and vascular access ports for investigating regiospecific intestinal absorption and hepatic elimination while requiring significantly lower doses of drugs. In addition, expression of certain cytochrome P450 enzymes and apical secretory and absorptive transporters in rabbit intestine is similar to that in humans making the rabbit a suitable model. METHODS: Individual 5-F Silastic catheters were placed in the proximal or distal portion of the small intestine or the colon of subject animals, while a 5-F Heparin Coated Polyurethane (HCP) catheter was implanted in the portal vein of each subject. The catheters were tunneled out of the abdomen and attached to separate subcutaneous access ports along the spine. The animals were allowed a two-week minimum recovery period prior to being used in pharmacokinetic studies. RESULTS AND DISCUSSION: After some initial difficulties, rabbits with IVAP implants proved to be an efficient and dependable model for investigating intestinal and hepatic extraction of drugs. Fluoroscopic visualization of intestinal and portal venous catheters indicated that surgically implanted catheters did not interfere with gastrointestinal motility or blood flow into the liver, respectively. Acute pH studies in the proximal portion of the small intestine were consistent with normal GI motility patterns.

Administration, Oral↗
PubMed1975

13-norleucine motilin versus pentagastrin: contrasting and competitive effects on gastrointestinal myoelectrical activity in the conscious dog.

In conscious fasted dogs, with chronically-implanted electrodes in stomach and small intestine, typical aborally-propagated interdigestive myoelectric complexes were induced by the infusion of 13-nor-leucine motilin (13-Nle-M); whereas when the normal interdigestive activity was abolished by the infusion of pentagastrin, the resulting 'postprandial' pattern of activity was not significantly modified by the administration of 13-Nle-M. Results from this study provide further evidence that Motilin as well as Gastrin may be involved in the control of gastrointestinal motility in dogs.

Animals↗
PubMed1997

Interstitial cells of Cajal as targets for pharmacological intervention in gastrointestinal motor disorders.

Interstitial cells of Cajal (ICCs) have recently been identified as the pacemaker cells for contractile activity of the gastrointestinal tract. These cells generate the electrical 'slow-wave' activity that determines the characteristic frequency of phasic contractions of the stomach, intestine and colon. Slow waves also determine the direction and velocity of propagation of peristaltic activity, in concert with the enteric nervous system. Characterization of receptors and ion channels in the ICC membrane is under way, and manipulation of slow-wave activity markedly alters movement of contents through the gut organs. Here Jan Huizinga, Lars Thuneberg, Jean-Marie Vanderwinden and Jüri Rumessen, suggest that, as ICCs are unique to the gut, they might be ideal targets for pharmacological intervention in gastrointestinal motility disorders, which are very common and costly.

Animals↗
PubMed2001

Effects of central and peripheral urocortin on fed and fasted gastroduodenal motor activity in conscious rats.

Since few previous studies have examined the effects of urocortin on physiological fed and fasted gastrointestinal motility, we administered urocortin intracerebroventricularly (icv) or intravenously (iv) in freely moving conscious rats and examined the changes in antral and duodenal motility. Icv and iv injection of urocortin disrupted fasted motor patterns of gastroduodenal motility, which were replaced by fed-like motor patterns. When urocortin was given icv and iv in the fed state, the motor activity remained like the fed patterns but % motor index (%MI) was decreased in the antrum and increased in the duodenum. Increase in the %MI in the duodenum induced by urocortin was shown as a nonpropagated event, since the transit of nonnutrient contents in the duodenum was decreased by icv and iv injection of urocortin. Changes in the gastroduodenal motility induced by icv injection of urocortin were abolished in animals with truncal vagotomy but not altered in animals with mechanical sympathectomy, suggesting that the vagal pathway may mediate the central action of urocortin. Neither urocortin antiserum nor alpha-helical CRF-(9-41) affected fed and fasted gastroduodenal motility, suggesting that endogenous urocortin is not involved in regulation of basal gastroduodenal motility.

Animals↗
PubMed2006

[The gastrointestinal motor function in irritable bowel syndrome (IBS)].

Irritable bowel syndrome (IBS) is presumed to be a gastrointestinal motility disorder with the brain-gut interaction. Psychological stress and stimuli of the colonic lumen increase colonic motor function which is exaggerated in IBS patients. Corticotropin-releasing hormone (CRH) is considered to be a major mediator of stress responses in the brain-gut interaction. Similarly, peripheral administration of CRH affects colonic motility, induces abdominal symptoms and stimulates ACTH secretion, all of which are exaggerated in IBS patients. CRH antagonist blocks the greater responses of colonic motility in IBS. CRH is a key peptide in the pathophysiology of IBS with the brain-gut interaction.

Animals↗
PubMed1989

Histamine as a central modulator of rat intestinal transit.

Histamine (HA) injected i.c.v. to rats inhibited intestinal propulsion in linear relation to the log of the administered doses (in the range from 20-100 micrograms/rat). In the same dose range HA also induced a dose-related analgesic effect (tail-flick test). The dose of HA maximally active by the i.c.v. route (100 micrograms/rat) showed neither of these effects when injected i.v. or i.p. HA-induced intestinal inhibition and analgesia were antagonized competitively by i.c.v. mepyramine (10 micrograms/rat), an H1 receptor antagonist, whereas cimetidine (10 micrograms/rat), an H2 receptor antagonist, had no effect. Repeated i.c.v. injections of HA resulted in tachyphylaxis of both intestinal inhibition and analgesia. Pretreatment with i.c.v. naloxone (20 micrograms/rat) antagonized the antipropulsive effect of HA in a noncompetitive fashion, but did not affect its antinociceptive action. The relevance of the central histaminergic system in the modulation of gastrointestinal motility and its relationship with the opioid system are discussed.

Analgesia↗
PubMed2001

Shorter postoperative atony after laparoscopic-assisted colonic resection? An animal study.

BACKGROUND: The duration of the postoperative ileus after laparoscopic surgery remains a controversial topic. The aim of our study was to compare the restoration of intestinal motility after laparoscopically assisted and conventional resection of the distal colon in a canine model. METHODS: Two weeks after the implantation of three electrodes on the jejunum, the distal colon was resected in a laparoscopic-assisted or conventional procedure in two groups of four dogs each. Gastrointestinal motility was monitored by registration of the electromyograhic activity of the small intestine and by intermittent fluoroscopies of radiopaque markers. RESULTS: Electrical activity in the early postoperative period was characterized by the basic electrical rhythm and the absence of spike activity. The first postoperative activity front of the migrating motility complex (MMC), indicating the restoration of motility, occurred significantly earlier after laparoscopic-assisted resection (4.5 +/- 1 hr) than after conventional resection (31 +/- 10 h). Radiological observations showed a significantly delayed gastric emptying and a prolonged transit of radiopaque markers to the rectum after open surgery. CONCLUSION: These results support the hypothesis that laparoscopic-assisted resection of the colon leads to a shortened postoperative atony in comparison to open surgery.

Animals↗
PubMed1978

Metoclopramide in gastrointestinal radiology.

Since the late 1960's, metoclopramide has been used in Europe for the treatment of gastrointestinal motility disorders. It is less well known in North America and its application in diagnostic radiology is unfamiliar to most radiologists. By comparing a control group of 103 patients with a study group of 86 patients, we found that intramuscular injection of metoclopramide is effective in reducing both gastric emptying time and small bowel transit time. Side effects were negligible in 125 patients. We also found the drug useful in gastric stasis, to differentiate between mechanical obstruction and motility disorders, in fluoroscopy of the terminal ileum, and in duodenal intubation.

Adolescent↗
PubMed2002

Antidiarrhoeal activity of Strychnos potatorum seed extract in rats.

The antidiarrhoeal activity of the methanol extract of the dried seeds of Strychnos potatorum (MESP) has been evaluated out in rats using different models (castor oil-induced diarrhoea, effects on gastrointestinal motility and on PGE(2)-induced gastric enteropooling. MESP (100, 200 and 400 mg/kg, p.o.) significantly (P<0.001) inhibited the frequency of defaecation and reduced the wetness of faecal droppings in castor oil-induced diarrhoea, decreased the propulsion of charcoal meal through the gastrointestinal tract, and also reduced the PGE(2)-induced enteropooling.

Animals↗
PubMed2006

A novel biomagnetic approach to study caecocolonic motility in humans.

Motility patterns play a major role in human colonic functions; however, its physiological significance is poorly understood. Several studies have been introducing the Alternating Current Biosusceptometry (ACB) as a valuable tool in gastroenterology and pharmaceutical research. Using gold standard techniques, great effort has been made to validate ACB as a method for measuring gastrointestinal motility in humans and animals. The aim of this study was to evaluate caecocolonic motility and its response to a meal in healthy volunteers. The results showed a dominant frequency of 3.17 +/- 0.13 cycles per minute (mean +/- SD) that remained unchanged even after a standardized meal (P > 0.01). The colonic response to a meal was recorded as a considerable increase in amplitude, reflected by motility index (P < 0.01) and was observed for all the volunteers. The caecocolonic motility could be assessed by the ACB providing new insights into physiological patterns of motility. Moreover, the method is non-invasive, radiation-free, cost-effective and independent of bowel preparation.

Adult↗
PubMed1987

Induction of phase 3 of the migrating motor complex in human small intestine by trimebutine.

The effects of trimebutine, a drug used in the treatment of various gastrointestinal motility disorders, have been investigated fed and fasted healthy subjects. Duodenojejunal motility was recorded manometrically with a 4-lumen probe. Trimebutine 50 or 100 mg was injected i.v. 3 or 25 min after observing a spontaneous Phase 3 complex in the fasted state. Other experiments were done in the postprandial state and after intravenous naloxone 0.8 mg. In the fasted state, trimebutine 100 mg, injected 25 min after a spontaneous Phase 3 complex consistently induced a premature Phase 3 complex. The mean duration of the migrating motor complex cycle decreased from 86.4 +/- 10.8 min to 32.5 +/- 1.0 min. Trimebutine 50 mg injected 3 and 25 min after a spontaneous Phase 3 complex did not significantly modify the periodicity of the migrating motor complex. Trimebutine 100 mg initiated Phase 3-like activity in the post-prandial state. Previous intravenous administration of naloxone 0.8 mg (Narcan) suppressed the stimulatory action of TMB. Thus, trimebutine is able to modify the motility pattern in the small intestine of man, possibly by acting at opioid receptors.

Adult↗
PubMed1993

Fat-induced ileal brake in humans: a dose-dependent phenomenon correlated to the plasma levels of peptide YY.

BACKGROUND: Upper gastrointestinal motility is regulated by the presence of nutrients in the distal gut. The present study evaluated whether lipid-induced ileal brake on gastric emptying (1) can be elicited by low fat concentrations; (2) is a dose-dependent phenomenon; and (3) is related to gastrointestinal peptide release. METHODS: Seven patients were studied in the defunctionalized stage of total colectomy, on three separate occasions. On each study day, patients ate a meal labeled in the solid component; 30 minutes later, one of the following solutions was randomly infused into the ileal pouch: 0.9% saline, 2% oleic acid, and 20% oleic acid. Plasma concentrations of peptide YY (PYY), enteroglucagon, neurotensin, and motilin were measured. RESULTS: Both oleic acid solutions slowed gastric emptying compared with saline (P < 0.001), the effect being dose dependent (P < 0.001). Ileal infusions did not modify neurotensin and enteroglucagon levels but induced a dose-dependent increase of PYY (P < 0.01) and a borderline decrease of motilin (P = 0.05) levels. Slower rates of gastric emptying were related to increased plasma concentrations of PYY (r = 0.615; P < 0.05). CONCLUSIONS: This study shows that (1) the ileal brake on gastric emptying can be evoked by low doses of lipids in the distal ileum; (2) the delay of gastric emptying is related to the release of PYY; and (3) both phenomena are dose dependent.

Adult↗
PubMed2004

The problem of gastric atony.

Normal gastrointestinal motility is crucial for maintaining an appropriate balance of microorganisms within the gut. Disruption of this system results in bacterial overgrowth and associated complications such as bacterial translocation, aspiration pneumonia, and sepsis. Critically ill animals are at increased risk of developing gastroparesis caused by primary gastrointestinal disturbances or severe metabolic derangements that impact gastrointestinal function. In the intensive-care setting, delayed gastric emptying complicates enteral nutrition, and the catabolic effects of severe illness further deplete the patient's caloric reserves, resulting in impaired wound healing, decreased immune function, and increased morbidity and mortality. The use of promotility drugs in critically ill patients is a safe, effective means to circumvent the problem of gastric atony and improve patient recovery. Understanding the drugs available and their interaction with the receptors involved in neuromuscular transmission within the gastrointestinal tract will aid the clinician in selecting the optimal prokinetic therapy.

Animals↗
PubMed1979

Methods for the analysis of intestinal function.

The intestinal tract, an organ of considerable complexity, requires application of numerous techniques for analysis of its physiology and perturbations by toxicologic agents. This review describes the methodology of importance in analysis of the absorptive function of the intestine and the transit of intestinal contents. Methods for studying absorption are categorized according to the technique for administering the test substance such as inclusion in the diet or by gastric and intestinal placement and the method of quantitating the degree of absorption such as determining the appearance of a test substance in systemic fluids or its disappearance from its site of administration in the intestine. In vitro techniques which have no in vivo analogs, such as the use of the everted sac, are briefly described and their limitations emphasized. Procedures of importance in the clinical diagnosis of malabsorption or in the experimental analysis of absorptive function in man are included and distinguished from techniques used in animal models. In addition, methods for studying aspects of gastrointestinal motility, including the use of luminal markers and analysis of the contractile and electrical activity of intestinal smooth muscle, are reviewed.

Animals↗
PubMed2006

Effect of laparoscopic versus open gastric bypass surgery on postoperative pain and bowel function.

BACKGROUND: This study was designed to assess postoperative pain and bowel function in morbidly obese patients undergoing Roux-en-Y gastric bypass (RYGBP) performed either by open or laparoscopic technique. METHODS: We prospectively studied patients scheduled for RYGBP between July 2002 and June 2003. Patients were assigned to the laparoscopic or open procedure by one surgeon. All patients received patient controlled analgesia (PCA) with intravenous morphine and rectal naproxen 500 mg every 12 hours. Postoperative analgesia was assessed daily using a visual analog scale (VAS) at rest, on walking and coughing. The amount of morphine used during the first 48 hours, the time of return of gastrointestinal motility and the time until first oral food intake were recorded. RESULTS: 53 patients were enrolled and studied (laparoscopic group n=33, open group n=20). Patients undergoing laparoscopic RYGBP requested less morphine (P=0.0001) and showed lower VAS pain scores than patients undergoing open RYGBP. The return of bowel movement in the laparoscopic group occurred 1 day earlier than in the open group (P=0.01). The time to first passage of gas (P=0.01) and oral food intake (P=0.06) was shorter after laparoscopic than after open RYGBP. Patients in the laparoscopic group were discharged 1(1/2) days earlier than patients in the open group (P=0.01). CONCLUSION: The laparoscopic RYGBP operation was associated with less postoperative pain and morphine consumption than the open RYGBP, thereby facilitating an earlier recovery of intestinal motility.

Administration, Rectal↗